Introduction: Pythons are a well-studied model of postprandial physiological plasticity. Consuming a meal evokes a suite of physiological changes in pythons including one of the largest documented increases in post-feeding metabolic rates relative to resting values. However, little is known about how this plasticity manifests in the brain. Previous work has shown that cell proliferation in the python brain increases 6 days following meal consumption. This study aimed to confirm these findings and build on them in the long term by tracking the survival and maturation of these newly created cells across a 2-month period. Methods: We investigated differences in neural cell proliferation in ball pythons 6 days after a meal with immunofluorescence using the cell-birth marker 5-bromo-12′-deoxyuridine (BrdU). We investigated differences in neural cell maturation in ball pythons 2 months after a meal using double immunofluorescence for BrdU and a reptilian ortholog of the neuronal marker Fox3. Results: We did not find significantly greater rates of cell proliferation in snakes 6 days after feeding, but we did observe more new cells in neurogenic regions in fed snakes 2 months after the meal. Feeding was not associated with higher rates of neurogenesis, but snakes that received a meal had higher numbers of newly created nonneuronal cells than fasted controls. We documented particularly high cell survival rates in the olfactory bulbs and lateral cortex. Conclusion: Consuming a meal stimulates cell proliferation in the brains of ball pythons after digestion is complete, although this effect emerged at a later time point in this study than expected. Higher rates of proliferation partially account for greater numbers of newly created non-neuronal cells in the brains of fed snakes 2 months after the meal, but our results also suggest that feeding may have a mild neuroprotective effect. We captured a slight trend toward higher cell survival rates in fed snakes, and survival rates were particularly high in brain regions associated with olfactory perception and processing. These findings shed light on the relationship between energy balance and the creation of new neural cells in the brains of ball pythons.

1.
Lieberwirth
C
,
Pan
Y
,
Liu
Y
,
Zhang
Z
,
Wang
Z
.
Hippocampal adult neurogenesis: its regulation and potential role in spatial learning and memory
.
Brain Res
.
2016
;
1644
:
127
40
.
2.
Berger
T
,
Lee
H
,
Young
AH
,
Aarsland
D
,
Thuret
S
.
Adult hippocampal neurogenesis in major depressive disorder and Alzheimer’s disease
.
Trends Mol Med
.
2020
;
26
(
9
):
803
18
.
3.
Redell
JB
,
Maynard
ME
,
Underwood
EL
,
Vita
SM
,
Dash
PK
,
Kobori
N
.
Traumatic brain injury and hippocampal neurogenesis: functional implications
.
Exp Neurol
.
2020
;
331
:
113372
.
4.
Gomes-Leal
W
.
Adult hippocampal neurogenesis and affective disorders: new neurons for psychic well-being
.
Front Neurosci
.
2021
;
15
:
594448
.
5.
Wakhloo
D
,
Oberhauser
J
,
Madira
A
,
Mahajani
S
.
From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer’s and Parkinson’s diseases
.
Neural Regen Res
.
2022
;
17
(
12
):
2606
14
.
6.
Birch
AM
,
Kelly
ÁM
.
Lifelong environmental enrichment in the absence of exercise protects the brain from age-related cognitive decline
.
Neuropharmacology
.
2019
;
145
(
Pt A
):
59
74
.
7.
Trinchero
MF
,
Herrero
M
,
Schinder
AF
.
Rejuvenating the brain with chronic exercise through adult neurogenesis
.
Front Neurosci
.
2019
;
13
:
1000
.
8.
Grońska-Pęski
M
,
Gonçalves
JT
,
Hébert
JM
.
Enriched environment promotes adult hippocampal neurogenesis through FGFRs
.
J Neurosci
.
2021
;
41
(
13
):
2899
910
.
9.
Okamoto
M
,
Mizuuchi
D
,
Omura
K
,
Lee
M
,
Oharazawa
A
,
Yook
JS
, et al
.
High-intensity intermittent training enhances spatial memory and hippocampal neurogenesis associated with BDNF signaling in rats
.
Cereb Cortex
.
2021
;
31
(
9
):
4386
97
.
10.
Briones
BA
,
Gould
E
.
Chapter 7: adult neurogenesis and stress
. In:
Fink
G
, editor.
Stress: physiology, biochemistry, and pathology
. 1st ed.
Cambridge, MA
:
Academic Press
;
2019
. p.
79
92
[cited 2023 Sep].
11.
Du Preez
A
,
Onorato
D
,
Eiben
I
,
Musaelyan
K
,
Egeland
M
,
Zunszain
PA
, et al
.
Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice
.
Brain Behav Immun
.
2021
;
91
:
24
47
.
12.
Vander Heiden
MG
,
Cantley
LC
,
Thompson
CB
.
Understanding the Warburg effect: the metabolic requirements of cell proliferation
.
Science
.
2009
;
324
(
5930
):
1029
33
.
13.
Beckervordersandforth
R
.
Mitochondrial metabolism-mediated regulation of adult neurogenesis
.
Brain Plast
.
2017
;
3
(
1
):
73
87
.
14.
Landry
T
,
Huang
H
.
Mini review: the relationship between energy status and adult hippocampal neurogenesis
.
Neurosci Lett
.
2021
;
765
:
136261
.
15.
Lee
J
,
Duan
W
,
Long
JM
,
Ingram
DK
,
Mattson
MP
.
Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats
.
J Mol Neurosci
.
2000
;
15
(
2
):
99
108
.
16.
Lee
J
,
Duan
W
,
Mattson
MP
.
Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice
.
J Neurochem
.
2002
;
82
(
6
):
1367
75
.
17.
Cao
S
,
Li
M
,
Sun
Y
,
Wu
P
,
Yang
W
,
Dai
H
, et al
.
Intermittent fasting enhances hippocampal NPY expression to promote neurogenesis after traumatic brain injury
.
Nutrition
.
2022
;
97
:
111621
.
18.
Bondolfi
L
,
Ermini
F
,
Long
JM
,
Ingram
DK
,
Jucker
M
.
Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice
.
Neurobiol Aging
.
2004
;
25
(
3
):
333
40
.
19.
Cardoso
A
,
Marrana
F
,
Andrade
JP
.
Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning
.
Neurobiol Learn Mem
.
2016
;
133
:
214
24
.
20.
Staples
MC
,
Fannon
MJ
,
Mysore
KK
,
Dutta
RR
,
Ongjoco
AT
,
Quach
LW
, et al
.
Dietary restriction reduces hippocampal neurogenesis and granule cell neuron density without affecting the density of mossy fibers
.
Brain Res
.
2017
;
1663
:
59
65
.
21.
Dicou
E
,
Attoub
S
,
Gressens
P
.
Neuroprotective effects of leptin in vivo and in vitro
.
Neuroreport
.
2001
;
12
(
18
):
3947
51
.
22.
Decressac
M
,
Wright
B
,
David
B
,
Tyers
P
,
Jaber
M
,
Barker
RA
, et al
.
Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis
.
Hippocampus
.
2011
;
21
(
3
):
233
8
.
23.
Chung
H
,
Li
E
,
Kim
Y
,
Kim
S
,
Park
S
.
Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells
.
J Endocrinol
.
2013
;
218
(
1
):
49
59
.
24.
Nieto-Estévez
V
,
Defterali
Ç
,
Vicario-Abejón
C
.
IGF-I: a key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain
.
Front Neurosci
.
2016
;
10
:
52
.
25.
Tofighi Zavareh
MA
,
Kargar Godaneh
MH
,
Eslahi
P
,
Aliaghaei
A
,
Asghari
MA
,
Azimzadeh
Z
, et al
.
Insulin can improve the normal function of the brain by preventing the loss of the neurons
.
J Cell Mol Anesth
.
2022 Fall
;
7
(
4
):
197
202
.
26.
Robertson
BA
,
Rathbone
L
,
Cirillo
G
,
D’Eath
RB
,
Bateson
M
,
Boswell
T
, et al
.
Food restriction reduces neurogenesis in the avian hippocampal formation
.
PLoS One
.
2017
;
12
(
12
):
e0189158
.
27.
MacDonald
IF
,
Kempster
B
,
Zanette
L
,
MacDougall-Shackleton
SA
.
Early nutritional stress impairs development of a song-control brain region in both male and female juvenile song sparrows (Melospiza melodia) at the onset of song learning
.
Proc Biol Sci
.
2006
;
273
(
1600
):
2559
64
.
28.
Ghaddar
B
,
Veeren
B
,
Rondeau
P
,
Bringart
M
,
Lefebvre d’Hellencourt
C
,
Meilhac
O
, et al
.
Impaired brain homeostasis and neurogenesis in diet-induced overweight zebrafish: a preventive role from A. borbonica extract
.
Sci Rep
.
2020
;
10
(
1
):
14496
.
29.
Paredes
MF
,
Sorrells
SF
,
Garcia-Verdugo
JM
,
Alvarez-Buylla
A
.
Brain size and limits to adult neurogenesis
.
J Comp Neurol
.
2016
;
524
(
3
):
646
64
.
30.
Secor
SM
.
Digestive physiology of the Burmese python: broad regulation of integrated performance
.
J Exp Biol
.
2008
;
211
(
Pt 24
):
3767
74
.
31.
Secor
SM
,
Diamond
J
.
Adaptive responses to feeding in Burmese pythons: pay before pumping
.
J Exp Biol
.
1995
;
198
(
Pt 6
):
1313
25
.
32.
Secor
SM
.
Gastric function and its contribution to the postprandial metabolic response of the Burmese python Python molurus
.
J Exp Biol
.
2003
;
206
(
Pt 10
):
1621
30
.
33.
Secor
SM
.
Evolutionary and cellular mechanisms regulating intestinal performance of Amphibians and reptiles
.
Integr Comp Biol
.
2005
;
45
(
2
):
282
94
.
34.
Cox
CL
,
Secor
SM
.
Matched regulation of gastrointestinal performance in the Burmese python, Python molurus
.
J Exp Biol
.
2008
;
211
(
Pt 7
):
1131
40
.
35.
Enok
S
,
Simonsen
LS
,
Wang
T
.
The contribution of gastric digestion and ingestion of amino acids on the postprandial rise in oxygen consumption, heart rate and growth of visceral organs in pythons
.
Comp Biochem Physiol Mol Integr Physiol
.
2013
;
165
(
1
):
46
53
.
36.
Secor
SM
,
Hicks
JW
,
Bennett
AF
.
Ventilatory and cardiovascular responses of a python (Python molurus) to exercise and digestion
.
J Exp Biol
.
2000
;
203
(
Pt 16
):
2447
54
.
37.
Habroun
SS
,
Schaffner
AA
,
Taylor
EN
,
Strand
CR
.
Food consumption increases cell proliferation in the python brain
.
J Exp Biol
.
2018
;
221
(
Pt 7
):
jeb173377
.
38.
Kim
KK
,
Adelstein
RS
,
Kawamoto
S
.
Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors
.
J Biol Chem
.
2009
;
284
(
45
):
31052
61
.
39.
McDonald
RP
,
Vickaryous
MK
.
Evidence for neurogenesis in the medial cortex of the leopard gecko, Eublepharis macularius
.
Sci Rep
.
2018
;
8
(
1
):
9648
.
40.
Holding
ML
,
Frazier
JA
,
Taylor
EN
,
Strand
CR
.
Experimentally altered navigational demands induce changes in the cortical forebrain of free-ranging northern pacific rattlesnakes (Crotalus o. oreganus)
.
Brain Behav Evol
.
2012
;
79
(
3
):
144
54
.
41.
Smeets
WJAJ
.
Distribution of dopamine immunoreactivity in the forebrain and midbrain of the snake Python regius: a study with antibodies against dopamine
.
J Comp Neurol
.
1988
;
271
(
1
):
115
29
.
42.
Bales
TB
.
Proliferation, migration, and survival of cells in the telencephalon of the ball python, Python regius [dissertation on the Internet]
.
San Luis Obispo
:
California Polytechnic State University
;
2014
[cited 2023 Sep]
43.
Font
E
,
Desfilis
E
,
Pérez-Cañellas
MM
,
García-Verdugo
JM
.
Neurogenesis and neuronal regeneration in the adult reptilian brain
.
Brain Behav Evol
.
2001
;
58
(
5
):
276
95
.
44.
Maine
AR
,
Powers
SD
,
Lutterschmidt
DI
.
Seasonal variation in cell proliferation and cell migration in the brain of adult red-sided garter snakes (Thamnophis sirtalis parietalis)
.
Brain Behav Evol
.
2014
;
84
(
3
):
181
96
.
45.
Pérez-Cañellas
MM
,
Font
E
,
García-Verdugo
JM
.
Postnatal neurogenesis in the telencephalon of turtles: evidence for nonradial migration of new neurons from distant proliferative ventricular zones to the olfactory bulbs
.
Brain Res Dev Brain Res
.
1997
;
101
(
1–2
):
125
37
.
46.
Secor
SM
.
Specific dynamic action: a review of the postprandial metabolic response
.
J Comp Physiol B
.
2009
;
179
(
1
):
1
56
.
47.
McCue
MD
,
Guzman
RM
,
Passement
CA
.
Digesting pythons quickly oxidize the proteins in their meals and save the lipids for later
.
J Exp Biol
.
2015
;
218
(
Pt 13
):
2089
96
.
48.
Garza
JC
,
Guo
M
,
Zhang
W
,
Lu
XY
.
Leptin increases adult hippocampal neurogenesis in vivo and in vitro
.
J Biol Chem
.
2008
;
283
(
26
):
18238
47
.
49.
Niewiarowski
PH
,
Balk
ML
,
Londraville
RL
.
Phenotypic effects of leptin in an ectotherm: a new tool to study the evolution of life histories and endothermy
.
J Exp Biol
.
2000
;
203
(
Pt 2
):
295
300
.
50.
González-Granero
S
,
Font
E
,
Desfilis
E
,
Herranz-Pérez
V
,
García-Verdugo
JM
.
Adult neurogenesis in the telencephalon of the lizard Podarcis liolepis
.
Front Neurosci
.
2023
;
17
:
1125999
.
51.
Pérez-Cañellas
MM
,
García-Verdugo
JM
.
Adult neurogenesis in the telencephalon of a lizard: a [3H]thymidine autoradiographic and bromodeoxyuridine immunocytochemical study
.
Brain Res Dev Brain Res
.
1996
;
93
(
1–2
):
49
61
.
52.
Marchioro
M
,
Nunes
JMAM
,
Ramalho
AMR
,
Molowny
A
,
Perez-Martinez
E
,
Ponsoda
X
, et al
.
Postnatal neurogenesis in the medial cortex of the tropical lizard Tropidurus hispidus
.
Neurosci
.
2005
;
134
(
2
):
407
13
.
53.
López-García
C
,
Molowny
A
,
Garcia-Verdugo
JM
,
Ferrer
I
.
Delayed postnatal neurogenesis in the cerebral cortex of lizards
.
Brain Res
.
1988
;
471
(
2
):
167
74
.
54.
Kaslin
J
,
Ganz
J
,
Brand
M
.
Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain
.
Philos Trans R Soc Lond B Biol Sci
.
2008
;
363
(
1489
):
101
22
.
55.
Font
E
,
García-Verdugo
JM
,
Alcántara
S
,
López-García
C
.
Neuron regeneration reverses 3-acetylpyridine-induced cell loss in the cerebral cortex of adult lizards
.
Brain Res
.
1991
;
551
(
1–2
):
230
5
.
56.
López-García
C
,
Molowny
A
,
Martínez Guijarro
FJ
,
Blasco-Ibáñez
JM
,
Luis de la Iglesia
JA
,
Bernabeu
A
, et al
.
Lesion and regeneration in the medial cerebral cortex of lizards
.
Histol Histopathol
.
1992
;
7
(
4
):
725
46
.
57.
López-García
C
,
Molowny
A
,
Nacher
J
,
Ponsoda
X
,
Sancho-Bielsa
F
,
Alonso-Llosa
G
.
The lizard cerebral cortex as a model to study neuronal regeneration
.
Acad Bras Cienc
.
2002
;
74
(
1
):
85
104
.
58.
Molowny
A
,
Nacher
J
,
López-García
C
.
Reactive neurogenesis during regeneration of the lesioned medial cerebral cortex of lizards
.
Neuroscience
.
1995
;
68
(
3
):
823
36
.
59.
Delgado-Gonzalez
FJ
,
Gonzalez-Granero
S
,
Trujillo-Trujillo
CM
,
García-Verdugo
JM
,
Damas-Hernandez
MC
.
Study of adult neurogenesis in the Gallotia galloti lizard during different seasons
.
Brain Res
.
2011
;
1390
:
50
8
.
60.
Hanusch
B
,
Ayanru
A
,
Powers
AS
.
Housing experience affects adult neurogenesis in turtles (Chrysemys picta)
.
Behav Neurosci
.
2021
;
135
(
1
):
24
31
.
61.
Austin
LE
,
Graham
C
,
Vickaryous
MK
.
Spontaneous neuronal regeneration in the forebrain of the leopard gecko (Eublepharis macularius) following neurochemical lesioning
.
Dev Dyn
.
2023
;
252
(
1
):
186
207
.
62.
Czéh
B
,
Welt
T
,
Fischer
AK
,
Erhardt
A
,
Schmitt
W
,
Müller
MB
, et al
.
Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis
.
Biol Psychiatry
.
2002
;
52
(
11
):
1057
65
.
63.
Prickaerts
J
,
Koopmans
G
,
Blokland
A
,
Scheepens
A
.
Learning and adult neurogenesis: survival with or without proliferation
.
Neurobiol Learn Mem
.
2004
;
81
(
1
):
1
11
.
64.
Zhang
F
,
Wang
S
,
Signore
AP
,
Chen
J
.
Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia
.
Stroke
.
2007
;
38
(
8
):
2329
36
.
65.
Giuliani
D
,
Galantucci
M
,
Neri
L
,
Canalini
F
,
Calevro
A
,
Bitto
A
, et al
.
Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease
.
Eur J Pharmacol
.
2014
;
740
:
144
50
.
66.
Yu
S
,
Baek
S
,
Brennan
RT
,
Bradley
CJ
,
Park
K
,
Lee
YS
, et al
.
Autophagic death of adult hippocampal neural stem cells following insulin withdrawal
.
Stem Cell
.
2008
;
26
(
10
):
2602
10
.
67.
Li
JW
,
Li
LL
,
Chang
LL
,
Wang
ZY
,
Xu
Y
.
Stem cell factor protects against neuronal apoptosis by activating AKT/ERK in diabetic mice
.
Braz J Med Biol Res
.
2009
;
42
(
11
):
1044
9
.
68.
Liao
GY
,
An
JJ
,
Gharami
K
,
Waterhouse
EG
,
Vanevski
F
,
Jones
KR
, et al
.
Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin
.
Nat Med
.
2012
;
18
(
4
):
564
71
.
69.
Hofer
MM
,
Barde
YA
.
Brain-derived neurotrophic factor prevents neuronal death in vivo
.
Nature
.
1988
;
331
(
6153
):
261
2
.
70.
Kalcheim
C
,
Gendreau
M
.
Brain-derived neurotrophic factor stimulates survival and neuronal differentiation in cultured avian neural crest
.
Brain Res
.
1988
;
469
(
1–2
):
79
86
.
71.
Rui
L
.
Brain regulation of energy balance and body weight
.
Rev Endocr Metab Disord
.
2013
;
14
(
4
):
387
407
.
72.
Pimentel
HC
,
Macêdo-Lima
M
,
Viola
GG
,
Melleu
FF
,
dos Santos
TS
,
Franco
HS
, et al
.
Telencephalic distributions of doublecortin and glial fibrillary acidic protein suggest novel migratory pathways in adult lizards
.
J Chem Neuroanat
.
2021
;
112
:
101901
.
73.
Pencea
V
,
Bingaman
KD
,
Freedman
LJ
,
Luskin
MB
.
Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain
.
Exp Neurol
.
2001
;
172
(
1
):
1
16
.
74.
Xie
Y
,
Li
Z
,
Du
J
,
Chen
Y
,
Chen
B
,
Wang
T
, et al
.
Visualization of rostral migratory stream in the developing rat brain by in vivo electroporation
.
Cell Mol Neurobiol
.
2018
;
38
(
5
):
1067
79
.
75.
Curtis
MA
,
Monzo
HJ
,
Faull
RLM
.
The rostral migratory stream and olfactory system: smell, disease and slippery cells
.
Prog Brain Res
.
2009
;
175
:
33
42
.
76.
Halpern
M
.
Nasal chemical senses in reptiles: structure and function
. In:
Gans
C
,
Crews
D
, editors.
Biology of the reptilia: hormones, brain, and behavior 18(E)
. 1st ed.
Chicago, IL
:
The University of Chicago Press
;
1992
. p.
423
523
.
77.
Schwenk
K
.
Of tongues and noses: chemoreception in lizards and snakes
.
Trends Ecol Evol
.
1995
;
10
(
1
):
7
12
.
78.
Kubie
JL
,
Vagvolgyi
A
,
Halpern
M
.
Roles of the vomeronasal and olfactory systems in courtship behavior of male garter snakes
.
J Comp Physiol Psychol
.
1978
;
92
(
4
):
627
41
.
79.
Halpern
M
,
Frumin
N
.
Roles of the vomeronasal and olfactory systems in prey attack and feeding in adult garter snakes
.
Physiol Behav
.
1979
;
22
(
6
):
1183
9
.
80.
Hoogland
PV
,
Vermeulen-Vanderzee
E
.
Efferent connections of the lateral cortex of the lizard Gekko gecko: evidence for separate origins of medial and lateral pathways from the lateral cortex to the hypothalamus
.
J Comp Neurol
.
1995
;
352
(
3
):
469
80
.
81.
Lanuza
E
,
Halpern
M
.
Afferent and efferent connections of the nucleus sphericus in the snake Thamnophis sirtalis: convergence of olfactory and vomeronasal information in the lateral cortex and the amygdala
.
J Comp Neurol
.
1997
;
385
(
4
):
627
40
.
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