Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Nucleus of the lateral olfactory tract: A hub linking the water homeostasis-associated supraoptic nucleus-arginine vasopressin circuit and neocortical regions to promote social behavior under osmotic challenge.

Homeostatic challenges may alter the drive for social interaction. The neural activity that prompts this motivation remains poorly understood. In the present study, we identify direct projections from the hypothalamic supraoptic nucleus to the cortico-amygdalar nucleus of the lateral olfactory tract (NLOT). Dual in situ hybridization with probes for pituitary adenylate cyclase-activating polypeptide (PACAP), as well as vesicular glutamate transporter (VGLUT)1, VGLUT2, V1a and V1b, revealed a population of vasopressin-receptive PACAPergic neurons in NLOT layer 2 (NLOT2). Water deprivation (48 h, WD48) increased sociability compared to euhydrated subjects, as assessed with the three-chamber social interaction test (3CST). Fos expression immunohistochemistry showed NLOT and its main efferent regions had further increases in rats subjected to WD48 + 3CST. These regions strongly expressed PAC1 mRNA. Microinjections of arginine vasopressin (AVP) into the NLOT produced similar changes in sociability to water deprivation, and these were reduced by co-injection of V1a or V1b antagonists along with AVP. We conclude that, during challenge to water homeostasis, there is a recruitment of a glutamatergic-multi-peptidergic cooperative circuit that promotes social behavior.

Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression.

Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behaviour, and fear responses. Here, we characterize the dynamics of expression changes of two key determinants for synaptic strength, the postsynaptic density (PSD) proteins AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), in response to in vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP ex vivo. Both long-term water deprivation in vivo, which powerfully upregulates AVPMNN metabolic activity, and exogenous AVP application ex vivo, in brain slices, significantly increased GluA1 and PSD95 expression as measured by western blotting, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.e., ventral hippocampus, amygdala and lateral habenula). By contrast, the visual cortex, a region not observed to receive AVPMNN projections, showed no such changes. Ex vivo application of V1a and V1b antagonists to ventral hippocampal slices ablated the AVP stimulated increase in postsynaptic protein expression measured by western blotting. Using a modified expansion microscopy technique, we were able to quantitatively assess the significant augmentation of PSD95 and GLUA1 densities in subcellular compartments in locus coeruleus tyrosine hydroxylase immunopositive fibres, adjacent to AVP axon terminals. Our data strongly suggest that the AVPMNN ascending system plays a role in the regulation of the excitability of targeted neuronal circuits through upregulation of key postsynaptic density proteins corresponding to excitatory synapses.

Microglial synaptic pruning on axon initial segment spines of dentate granule cells: Sexually dimorphic effects of early-life stress and consequences for adult fear response.

Axon initial segments (AIS) of dentate granule cells in the hippocampus exhibit prominent spines (AISS) during early development that are associated with microglial contacts. In the present study, we investigated whether developmental changes in AISS could be modified by early-life stress (ELS), specifically neonatal maternal separation (MS), through stress hormones and microglial activation and examined the potential behavioural consequences. We examined AISS at postnatal day (PND)5, 15 and 50, using Golgi-Cox staining and anatomical analysis. Neurone-microglial interaction was assessed using antibodies against ankyrin-G, PSD-95 and Iba1, for AIS, AISS and microglia visualisation, respectively, in normally reared and neonatal maternally separated male and female rats. We observed a higher density of AISS in ELS rats at both PND15 and PND50 compared to controls. Effects were more pronounced in females than males. AIS-associated microglia in ELS rats showed a hyper-ramified morphology and less co-localisation with PSD-95 compared to controls at PND15. ELS-associated alteration in microglial morphology and synaptic pruning was mimicked by treatment of acute hippocampal slices of normally reared rats with vasopressin. ELS rats exhibited increased freezing behaviour during auditory fear memory testing, which was more pronounced in female subjects and corresponded with increased Fos expression in dorsal and ventral dentate granule cells. Thus, microglial synaptic pruning in dentate AIS of hippocampus is influenced by ELS, with demonstrable sex bias regarding its anatomical characteristics and subsequent fear-induced defensive behaviours.

ACE2 in the second act of COVID-19 syndrome: Peptide dysregulation and possible correction with oestrogen.

Coronavirus disease 2019 (COVID-19) has become the most critical pandemic of the 21st Century and the most severe since the 1918 influenza pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the host by binding to angiotensin-converting enzyme 2 (ACE2). The role of ACE2 in the pathophysiology of coronavirus disease 2019 (COVID-19) is a topic of debate, with clinical and experimental evidence indicating a multifaceted relationship between ACE2 activity and disease severity. Here, we review the mechanisms by which the peptidergic substrates and products of ACE and ACE2 contribute to physiological and pathophysiological processes and hypothesise how down-regulation of ACE2 by SARS-CoV-2 cellular entry disrupts homeostasis. A better understanding of the endocrinology of the disease, in particular the neuroendocrinology of ACE2 during COVID-19, may contribute to the timely design of new therapeutic strategies, including the regulation of ACE2 itself by steroid hormones, to ameliorate the severity of COVID-19.

Behavioral role of PACAP signaling reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations.

The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAP role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing Fos activation of brain neurons after olfactory threat cue in wild-type and PACAP knockout mice. Neuronal activation and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply downregulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.

VGLUT-VGAT expression delineates functionally specialised populations of vasopressin-containing neurones including a glutamatergic perforant path-projecting cell group to the hippocampus in rat and mouse brain.

The origin and functional significance of vasopressin (AVP)-containing fibres in limbic regions has been an ongoing subject of investigation for several years. We have previously identified AVP-magnocellular neurones of rat hypothalamus that provide glutamatergic projections to the hippocampus, amygdala, lateral habenula and locus coeruleus. However, we also reported AVP-immunopositive fibres in those regions that are thin and make Gray type II synapses, which are unlikely to be of magnocellular origin. Therefore, in the present study, we characterised AVP mRNA co-expression with expression of mRNAs marking glutamatergic (vesicular glutamate transporter [VGLUT]) and GABAergic (vesicular GABA transporter [VGAT]) neuronal traits in rat and mouse brain, using high-resolution in situ hybridisation methods, including a radio-ribonucleotide and RNAscope 2.5 HD duplex assay, with Slc17a7, Slc17a6, Slc32a1 and Avp probes corresponding to mRNAs of VGLUT1, VGLUT2, VGAT and AVP, respectively. We located 18 cell groups expressing Avp and identified their molecular signatures for VGLUT and VGAT mRNA expression. Avp cell groups of hypothalamus and midbrain are mainly VGLUT mRNA-expressing, whereas those in regions derived from cerebral nuclei are mainly VGAT mRNA-expressing, suggesting a functional segregation of glutamate/GABA co-transmission with AVP. A newly identified Slc17a7 and Slc17a6 (but not Slc32a1) expressing vasopressinergic cell group was found in layer II-III neurones of the central entorhinal cortex, which projects to the hippocampus. These data support the notion of a complex role for AVP with respect to modulating multiple central circuits controlling behaviour in specific ways depending on co-transmission with glutamate or GABA, potentially giving rise to a functional classification of AVPergic neurones in the central nervous system.

A Synaptically Connected Hypothalamic Magnocellular Vasopressin-Locus Coeruleus Neuronal Circuit and Its Plasticity in Response to Emotional and Physiological Stress.

The locus coeruleus (LC)-norepinephrine (NE) system modulates a range of salient brain functions, including memory and response to stress. The LC-NE system is regulated by neurochemically diverse inputs, including a range of neuropeptides such as arginine-vasopressin (AVP). Whilst the origins of many of these LC inputs, their synaptic connectivity with LC neurons, and their contribution to LC-mediated brain functions, have been well characterized, this is not the case for the AVP-LC system. Therefore, our aims were to define the types of synapses formed by AVP+ fibers with LC neurons using immunohistochemistry together with confocal and transmission electron microscopy (TEM), the origins of such inputs, using retrograde tracers, and the plasticity of the LC AVP system in response to stress and spatial learning, using the maternal separation (MS) and Morris water maze (MWM) paradigms, respectively, in rat. Confocal microscopy revealed that AVP+ fibers contacting tyrosine hydroxylase (TH)+ LC neurons were also immunopositive for vesicular glutamate transporter 2, a marker of presynaptic glutamatergic axons. TEM confirmed that AVP+ axons formed Gray type I (asymmetric) synapses with TH+ dendrites thus confirming excitatory synaptic connections between these systems. Retrograde tracing revealed that these LC AVP+ fibers originate from hypothalamic vasopressinergic magnocellular neurosecretory neurons (AVPMNNs). MS induced a significant increase in the density of LC AVP+ fibers. Finally, AVPMNN circuit upregulation by water-deprivation improved MWM performance while increased Fos expression was found in LC and efferent regions such as hippocampus and prefrontal cortex, suggesting that AVPMMN projections to LC could integrate homeostatic responses modifying neuroplasticity.

A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling.

The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2. This cell type is anatomically located to receive afferents from midbrain reward (dopamine and serotonin) and hypothalamic water and energy homeostasis (vasopressin and orexin) circuits. These afferents shared the expression of estrogen synthase (aromatase) and VGLUT2, both in their somata and axon terminals. We demonstrate dynamic changes in LHbM VGAT+ cell density, dependent upon gonadal functional status, that closely correlate with motivational behavior in response to predator and forced swim stressors. The findings suggest that the homeostasis and reward-related glutamatergic convergent projecting pathways to LHbMC employ a localized neurosteroid signaling mechanism via axonal expression of aromatase, to act as a switch for GERN excitation/inhibition output prevalence, influencing depressive or motivated behavior.

Dynamic Modulation of Mouse Locus Coeruleus Neurons by Vasopressin 1a and 1b Receptors.

The locus coeruleus (LC) is a brainstem nucleus distinguished by its supply of noradrenaline throughout the central nervous system. Apart from modulating a range of brain functions, such as arousal, cognition and the stress response, LC neuronal excitability also corresponds to the activity of various peripheral systems, such as pelvic viscera and the cardiovascular system. Neurochemically diverse inputs set the tone for LC neuronal activity, which in turn modulates these adaptive physiological and behavioral responses essential for survival. One such LC afferent system which is poorly understood contains the neurohormone arginine-vasopressin (AVP). Here we provide the first demonstration of the molecular and functional characteristics of the LC-AVP system, by characterizing its receptor-specific modulation of identified LC neurons and plasticity in response to stress. High resolution confocal microscopy revealed that immunoreactivity for the AVP receptor 1b (V1b) was located on plasma membranes of noradrenergic and non-noradrenergic LC neurons. In contrast, immunoreactivity for the V1a receptor was exclusively located on LC noradrenergic neurons. No specific signal, either at the mRNA or protein level, was detected for the V2 receptor in the LC. Clusters immunoreactive for V1a-b were located in proximity to profiles immunoreactive for GABAergic and glutamatergic synaptic marker proteins. AVP immunopositive varicosities were also located adjacent to labeling for such synaptic markers. Whole-cell patch clamp electrophysiology revealed that the pharmacological activation of V1b receptors significantly increased the spontaneous activity of 45% (9/20) of recorded noradrenergic neurons, with the remaining 55% (11/20) of cells exhibiting a significant decrease in their basal firing patterns. Blockade of V1a and V1b receptors on their own significantly altered LC neuronal excitability in a similar heterogeneous manner, demonstrating that endogenous AVP sets the basal LC neuronal firing rates. Finally, exposing animals to acute stress increased V1b, but not V1a receptor expression, whilst decreasing AVP immunoreactivity. This study reveals the AVP-V1a-b system as a considerable component of the LC molecular architecture and regulator of LC activity. Since AVP primarily functions as a regulator of homeostasis, the data suggest a novel pathway by modulating the functioning of a brain region that is integral to mediating adaptive responses.

Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping.

The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA). The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS), consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

Thirst Is Associated with Suppression of Habenula Output and Active Stress Coping: Is there a Role for a Non-canonical Vasopressin-Glutamate Pathway?

Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP) is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair, respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients.

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

Extra-neurohypophyseal axonal projections from individual vasopressin-containing magnocellular neurons in rat hypothalamus.

Conventional neuroanatomical, immunohistochemical techniques, and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP)-containing magnocellular neurons (magnocells) in the hypothalamic paraventricular nucleus (PVN). Here, we used in vivo extracellular recording, juxtacellular labeling, post-hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus (SCN), lateral habenula (LHb), medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an "occasional" phenomenon as previously thought.

Differential effects of osmotic and SSR149415 challenges in maternally separated and control rats: the role of vasopressin on spatial learning.

Maternal separation (MS) has been demonstrated to up-regulate the hypothalamic vasopressin (VP) system. Intracerebrally released VP has been demonstrated to affect several types of animal behaviour, such as active/passive avoidance, social recognition, and learning and memory. However, the role of VP in spatial learning remains unclear. In the present study, we investigated the effects of an osmotic challenge and a V1b receptor-specific (V1bR) antagonist, SSR149415, on spatial learning of maternally separated and animal facility reared (AFR) adult male Wistar rats. The osmotic challenge was applied by injecting a hypertonic saline solution, 1h before the Morris water maze test (MWM). V1bR antagonist SSR149415 (5mg/kg) was injected i.p. twice (1h and 30 min) previous to the MWM. A combined treatment with both osmotic challenge and the SSR149415 was applied to the third group whereas rats for basal condition were injected with isotonic saline. Under basal condition no differences between AFR and MS groups were observed. MS rats showed severe impairment during the MWM after the osmotic challenge, but not after the administration of SSR149415. For AFR rats, the opposite phenomenon was observed. The joint application of SSR149415 and osmotic challenge restored the spatial learning ability for both groups. The differential impairment produced by osmotic stress-induced up-regulation and SSR149415 induced V1bR blockage in MS and control rats suggested that VP involvement in spatial learning depends on the individual intrinsic ligand-receptor functional state.

Glial activation in a pilocarpine rat model for epileptogenesis: a morphometric and quantitative analysis.

In this work we examined the correlation between long-term glial resilience and slow epileptogenesis using the pilocarpine-insult rat model. We assessed, quantitatively and morphometrically, glial fibrillary acidic protein (GFAP) expression and cell densities in hippocampus in a dose-response manner 2, 4 and 8 weeks after the pilocarpine insult. GFAP changes were correlated with observations on microglial activation. We used a commonly applied epileptogenic pilocarpine dose (380mg/kg) and its fractions of 1/10, 1/4 and 1/2. GFAP expression evaluated at 2 weeks revealed dose-dependent cytoskeletal hypertrophy and loss of GFAP+ cell densities in hippocampus. At 4-week timepoint, recoveries of the above mentioned parameters were observed in all groups, except for the full dose group in which the astrocytic hypertrophy reached the highest level, while its density dropped to the lowest level. Strong and localized microgliosis revealed by CD11b immunoreactivity was observed in hilus in the full dose group at 2- and 4-, persisting at 8-week timepoints. Through changing pattern analysis, we conclude that the loss of astroglial resilience is likely to be a determining factor for spontaneous recurrent seizure onset.

Astrogliosis is temporally correlated with enhanced neurogenesis in adult rat hippocampus following a glucoprivic insult.

2-Deoxy-d-glucose (2-DG) administration causes transient depletion of glucose derivates and ATP. Hence, it can be used in a model system to study the effects of a mild glycoprivic brain insult mimicking transient hypoglycemia, which often occurs when insulin or oral hypoglycemic agents are administered for diabetes control. In the present study, the effect of a single 2-DG application (500mg/kg, a clinically applicable dose) on glial reactivity and neurogenesis in adult rat hippocampus was examined, as well as a possible temporal correlation between these two phenomena. Post-insult (PI) glial reactivity time course was assessed by immunoreaction against glial-fibrillary acidic protein (GFAP) during the following 5 consecutive days. A clear increase of GFAP immunoreactivity in hilus was observed from 48 to 96h PI. Moreover, enhanced labeling of long radial processes in the granule cell layer adjacent to hilus was evidenced. On the other hand, a transient increase of progenitor cell proliferation was detected in the subgranular zone, prominently at 48h PI, coinciding with the temporal peak of glial activation. This increase resulted in an augment of neuroblasts double labeled with 5-bromo-deoxyuridine (BrdU) and with double cortin (DCX) at day 7 PI. Around half of these cells survived 28 days showing matured neuronal phenotype double labeled by BrdU and a neuronal specific nuclear protein marker (NeuN). These findings suggest that a transient neuroglycoprivic state exerts a short-term effect on glial activation that possibly triggers a long-term effect on neurogenesis in hippocampus.