Hippocampus
-
The Wistar Audiogenic Rat (WAR) is an epileptic-prone strain developed by genetic selection from a Wistar progenitor based on the pattern of behavioral response to sound stimulation. Chronic acoustic stimulation protocols of WARs (audiogenic kindling) generate limbic epileptogenesis, confirmed by ictal semiology, amygdale, and hippocampal EEG, accompanied by hippocampal and amygdala cell loss, as well as neurogenesis in the dentate gyrus (DG). In an effort to identify genes involved in molecular mechanisms underlying epileptic process, we used suppression-subtractive hybridization to construct normalized cDNA library enriched for transcripts expressed in the hippocampus of WARs. ⋯ Although semiquantitative RT-PCR analysis shows that the hippocampal levels of the GluR2 subunits do not differ between naïve WARs and their Wistar counterparts, we observed that the expression of the transcript encoding the splice-variant GluR2-flip is increased in the hippocampus of WARs submitted to both acute and kindled audiogenic seizures. Moreover, using in situ hybridization, we verified upregulation of GluR2-flip mainly in the CA1 region, among the hippocampal subfields of audiogenic kindled WARs. Our findings on differential upregulation of GluR2-flip isoform in the hippocampus of WARs displaying audiogenic seizures is original and agree with and extend previous immunohistochemical for GluR2 data obtained in the Chinese P77PMC audiogenic rat strain, reinforcing the association of limbic AMPA alterations with epileptic seizures.
-
Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with senile beta-amyloid (Abeta) plaques and cognitive decline. Neurogenesis in the adult hippocampus is implicated in regulating learning and memory, and is increased in human postmortem brain of AD patients. However, little is currently known about the changes of hippocampal neurogenesis in the progression of AD. ⋯ The number of hippocampal BrdU-positive cells and BrdU-positive cells differentiating into neurons (neurogenesis) in 10-month-old mice was greater in transgenic mice compared with age-matched controls, but the ratio of hippocampal BrdU-positive cells differentiating into neurons and astroglia was comparable. These results suggest hippocampal neurogenesis may increase during the progression of AD. Targeting this change in neurogenesis and understanding the underlying mechanism could lead to the development of a new treatment to control the progression of AD.
-
Cholinergic and GABAergic neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) projecting to the hippocampus, constitute the septohippocampal projection, which is important for hippocampal-dependent learning and memory. There is also evidence for an extrinsic as well as an intrinsic glutamatergic network within the MS/vDB. GABAergic and cholinergic septohippocampal neurons express the serotonergic 5-HT(1A) receptor and most likely also glutamatergic NMDA receptors. ⋯ In conclusion, septal 5-HT(1A) receptors appears to play a more prominent role in emotional than in spatial memory. Importantly, septal 5-HT(1A) and NMDA receptors appear to interact in a manner, which is particularly critical for the expression or retrieval of hippocampal-dependent long-term spatial memory. It is proposed that NMDA receptor hypofunction in the septal area may unmask a negative effect of 5-HT(1A) receptor activation on memory, which may be clinically relevant.
-
The aim of this study was to investigate the effect of spider toxins on brain injury induced by oxygen deprivation and low glucose (ODLG) insult on slices of rat hippocampus. After ODLG insult cell viabilility in hippocampal slices was assessed by confocal microscopy and epifluorescence using the live/dead kit containing calcein-AM and ethidium homodimer and CA1 population spike amplitude recording during stimulation of Schaffer collateral fibers. Spider toxins Tx3-3 or Tx3-4 and conus toxins, omega-conotoxin GVIA or omega-conotoxin MVIIC are calcium channel blockers and protected against neuronal damage in slices subjected to ODLG insult. ⋯ During the ischemic insult, glutamate release from slices was increased by 71% (from 7.0 +/- 0.3 nM/mg of protein control slices not subjected to ischemia to 12 +/- 0.4 nM/mg of protein in slices exposed to ischemia). Tx3-3, Tx3-4, omega-conotoxin GVIA or omega-conotoxin MVIIC inhibited the ischemia-induced increase on glutamate release by 54, 72, 60, and 70%, respectively. Thus Tx3-3 and Tx3-4 provided robust ischemic neuroprotection showing potential as a novel class of agent that exerts neuroprotection in an in vitro model of brain ischemia.
-
Voluntary physical activity induces molecular changes in the hippocampus consistent with improved hippocampal function, but few studies have explored the effects of wheel running on specific hippocampal-dependent learning and memory processes. The current studies investigated the impact of voluntary wheel running on learning and memory for context and extinction using contextual fear conditioning which is known to be dependent on the hippocampus. When conditioning occurred prior to the start of 6 weeks of wheel running, wheel running had no effect on memory for context or extinction (assessed with freezing). ⋯ The effect of wheel running on brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in hippocampal and amygdala subregions was also investigated. Wheel running increased BDNF mRNA in the dentate gyrus, CA1, and the basolateral amygdala. Results are consistent with improved hippocampal function following physical activity.