Differential impact of chronic stress along the hippocampal dorsal–ventral axis

First published online 06 February 2014Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.Pinto V and Mota C were supported by Fundacao para a Ciencia e Tecnologia (FCT) grants (SFRH/BPD/69132/2010; SFRH/BD/81881/2011, respectively). This work was supported by an FCT grant (PTDC/SAU-NSC/120590/2010). The authors declare no competing financial interests

Retinoic Acid Restores Adult Hippocampal Neurogenesis and Reverses Spatial Memory Deficit in Vitamin A Deprived Rats

A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function

THE EFFECT OF THEOPHYLLINE AND IMMOBILIZATION STRESS ON HALOPERIDOL-INDUCED CATALEPSY AND ON METABOLISM IN THE STRIATUM AND HIPPOCAMPUS, STUDIED WITH LACTOGRAPHY

Whether inducing catalepsy in the rat by an intraperitoneal injection of haloperidol (0.5 mg/kg) had an effect on metabolism in the striatum and in the hippocampus, as determined by lactography, and whether reducing the cataleptic state with stress or theophylline (8 mg/kg i.v.) had any impact on metabolism in these two regions of the brain was investigated. Furthermore, whether theophylline reduced catalepsy in rats through the adrenals was investigated. Haloperidol caused a significant increase in the metabolism of lactate, both in the striatum and in the hippocampus. Reducing haloperidol-induced catalepsy with short-term immobilisation stress did not affect the metabolism of lactate, neither in the striatum nor in the hippocampus. Reducing haloperidol-induced catalepsy with theophylline caused a significant rise in the metabolism of lactate in the striatum, while no effect was seen in the hippocampus. Adrenalectomy did not compromise the anti-cataleptic property of theophylline. It is concluded theophylline is a potent antagonist of haloperidol-induced catalepsy, and that this effect is not mediated by the adrenals. Furthermore, it is reported that haloperidol influenced metabolism in regions of the brain not considered to be its primary target. Lactography is considered to be a very useful tool in the study of metabolism during activity

Exposure to chronic psychosocial stress and corticosterone in the rat:Effects on spatial discrimination learning and hippocampal protein kinase C gamma immunoreactivity

Previous reports have demonstrated a striking increase of the immunoreactivity of the gamma-isoform of protein kinase C (PKC gamma-ir) in Ammon's horn and dentate gyrus (DC) of rodent hippocampus after training in a spatial orientation task. In the present study, we investigated how 8 days of psychosocial stress affects spatial discrimination learning in a hole board and influences PKC gamma-ir in the hippocampal formation. The acquisition of both reference memory and working memory was significantly delayed in the stressed animals during the entire training period. With respect to cellular plasticity, the training experience in both nonstressed and stressed groups yielded enhanced PKC gamma-ir in the CA1 and CA3 regions of the posterior hippocampus but not in subfields of the anterior hippocampus. Stress enhanced PKC gamma-ir in the DG and CA3 pyramidal cells of the anterior hippocampus. In stressed animals that were subsequently trained, the PKC gamma-ir was increased in the posterior CA1 region to the same level as that found in nonstressed trained animals. Stress apparently abrogated the PKC gamma-ir training response in the CA3 region. In a second experiment, the elevation of plasma corticosterone levels to values that are found during stress did not significantly influence reference memory scores but slightly and temporarily affected working memory. The training-induced enhancement of PKC gamma-ir in the CA1 region was similar in trained and corticosterone-treated trained animals, but the learning-induced PKC gamma-ir response in the posterior CA3 area was absent after corticosterone pretreatment. These results reveal that prolonged psychosocial stress causes spatial learning deficits, whereas artificial elevation of corticosterone levels to the levels that occur during stress only mildly affects spatial memory performance. The spatial learning deficits following stress are reflected only in part in the redistribution of hippocampal PKC gamma-ir following training. (C) 1997 Wiley-Liss, Inc