Effects of Beta; 1-adrenoceptors in the Basolateral Amygdala on Spatial Memory, Passive Avoidance, Long-term Potentiation and Neuronal Arborization in the Hippocampal CA1 Region in Response to Unavoidable Stress

Abstract Norepinephrine in the basolateral amygdala (BLA) plays a pivotal role in mediating the effects of stress on memory functions in the hippocampus, however, the functional contribution of β1-adrenergic receptors on the BLA inputs to the CA1 region of hippocampus and memory function are not well understood. In the present study the role of β1-adrenoreceptor in the BLA on memory, neuronal arborization and long-term potentiation (LTP) in the CA1 region of hippocampus was examined by infusion the β1-adrenoreceptor agonist (Dobutamine; 0.5µl/side) or antagonist (Atenolol; 0.25µL/side) bilaterally into the BLA before foot-shock stress. Passive avoidance test results showed that Step-through latency time was significantly decreased in the stress group rats one, four and seven days after the stress, which intra-BLA injection of Atenolol or Dobutamine before stress couldn't attenuate this reduction. Barnes-maze results revealed that infusion of Dobutamine and Atenolol significantly reduced spatial memory indicators such as increased latency time, the number of errors and the distance traveling to achieve the target hole in the stress group. These learning impairments in stress rats correlated with a reduction of LTP in hippocampal CA1 synapses in-vivo, which infusion of Dobutamine and Atenolol couldn't attenuate the population spike amplitude and mean-field excitatory postsynaptic potentials (fEPSP) slope reduction induced by stress. Also, the Golgi-Cox staining demonstrated that infusion of Atenolol attenuated stress decreased CA1 region dendritic and axonal arborization. These results suggest that β1-adrenergic receptors activation or block seem to exacerbate stress-induced hippocampal memory deficits and this effect is independent of CA1 LTP modulation.

Gastrodin improves hippocampal neurogenesis by NO-cGMP-PKG signaling pathway in cerebral ischemic mice / 中国中药杂志

This paper was aimed to investigate the effect of gastrodin( GAS) on hippocampal neurogenesis after cerebral was chemic and to explore its mechanism of action related to NO. The cerebral ischemia model of C57 BL/6 mice was established by bilateral common carotid artery occlusion. The pathological changes in hippocampal CA1 region and the cognitive function of mice were assessed by HE staining and Morris water maze test,respectively. The count of Brd U/Neu N positive cells in dentate gyrus was detected by immunofluorescence assay. The NOS activity and the NO content were determined by colorimetric and nitrate reduction methods,respectively.The level of c GMP was measured by ELISA kit,and the PKG protein expression was tested by Western blot. On postoperative day 8,the hippocampal CA1 pyramidal neurons of mice showed irregular structure,with obvious nuclear pyknosis,loose cell arrangement and obvious decrease in the number of neurons. On postoperative day 29,the spatial learning ability and memory were decreased. These results indicated cerebral ischemia in mice. Meanwhile,the Brd U/Neu N positive cells were increased significantly in ischemic mice,indicating that neurogenesis occurred in hippocampus after cerebral ischemia. Treatment with different doses of gastrodin( 50 and 100 mg·kg-1) significantly ameliorated the pathological damages in the CA1 region,improved the ability of learning and memory,and promoted hippocampal neurogenesis. At the same time,both the NOS activity and the NO concentration were decreased in model group,but the c GMP level was increased,and the PKG protein expression was up-regulated. Gastrodin administration activated the NOS activity,promoted NO production,further increased c GMP level and up-regulated PKG protein expression. These results suggested that gastrodin can promote hippocampal neurogenesis after cerebral ischemia and improve cognitive function in mice,which may be related to the activation of NO-cGMP-PKG signaling pathway.

Effect of human chorionic gonadotropin and vitamine E on cellular density of CA1 hippocampal area, learning ability and memory, following ischemia - reperfusion injury in mice

Reduction in cerebral blood flow following cereblal ischemia cause the production of oxygen free radicals and finally leads to brain tissue destruction. Pyramidal cells of the CA1 region of hippocampus are highly sensitive to hypoxic condition. This study was done to determine the effect of human chorionic gonadotropin [hCG] and vitamine E on cellular density of CA1 hippocampal area, learning ability and memory, following ischemia - reperfusion injury in mice. This experimental study was done on 40 male mice in 5 groups as follow: sham control, ischemia, hCG treated, vitamine E treated and hCG + vitamine E treated groups. Single dose of vitamin E was injected intraperitonaly during the establishment of reperfusion and hCG was injected from 48h after ischemia for 5 days. Folowing the treatment period, mice brains were fixated by transcardial perfusion and stained by nissle method. The shuttle box was used to evaluate the learning memory. Co-administartion of vitamine E and hCG, significantly increased the cell numbers in hippocampus compared to the ischemic group [P<0.001]. Also learning and memory improved in treatment group in comparison with ischemia group [P<0.05]. Co-administration of vitamin E and hCG improved ischemia-induced neurodegenration and memory impairment

Intrahippocampal injection of 3 alpha diol [a testosterone metabolite] and indomethacin [3 alpha -HSD blocker], impair acquisition of spatial learning and memory in adult male rats

Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3 alpha diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3 alpha diol [0.2, 1, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [1.5, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [3 micro g/ 0.5 micro L/side] + 3 alpha diol [1 micro g/ 0.5 micro L/side], 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3 alpha diol [1, 3 and 6 micro g/ 0.5 micro L/side] and indomethacin [3 and 6 micro g/ 0.5 micro L/side] significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3 alpha diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3 alpha diol could not change spatial learning and memory impairment effect of indomethacin or 3 alpha diol in Morris Water Maze task

[Neurotrophic effect of tacrolimus on pyramidal cells of CA1 region of hippocampus following transient global ischemia/reperfusion in male wistar rat]

Cerebral ischemia is known as a major problem in the world. Reperfusion following the ischemia ultimately leads to programmed cell death or apoptosis. Specific regions of the brain and certain types of neurons are more susceptible to cerebral ischemia, such as pyramidal neurons of CA1 region of hippocampus. Recently, using of immunophilin ligands has been considered to be a potential and appropriate strategy for neuroprotective and neurogenitor activity. Up to now, the right time of injection for providing the suitable effect on pyramidal cells of CA1 has not been assessed precisely. In this study, the neurotrophic effects of tacrolimus on CA1 cells were studied on 40 male Wistar rats in 8 experimental groups. Ischemia model was induced by ligation of bilateral common carotid arteries. For detecting the most appropriate time for 6mg/kg, Injection was done via single and double doses with intervals of 6, 24, 48 and hours. The repeated doses of 6mg/kg with interval of 48 hours are the suitable dose and time of injection. It seems that tacrolimus can be an appropriate strategy as a neurotrophic drug for treating brain ischemia

Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

Reduced hippocampal GABAergic function in Wistar audiogenic rats

Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19 percent and its maximum slope by 73 ± 21 percent. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46 percent) or slope (11 ± 29 percent). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.

[Influence of intracerebral administration of l-arginine in dorsal hippocampus [CA1] on win55, 212-2 induced state-dependent memory]

Cannabinoids are a class of psychoactive compounds that produce a wide array of effects in a large number of species. In the present study, the effects of bilateral intra-CA1 injections of L-arginine on WIN55, 212-2 induced state-dependent memory of passive avoidance task was examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intraCA1 administration of cannabinoid receptor agonist, WIN55, 212-2 [0.5 and 1 micro g/mouse], decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 [1micro g/mouse]was restored by pre-test administration of the same dose of the drug, showing the state-dependent memory of WIN55, 212-2. Single intra-CA1 administration of L-arginine [0.3, 1 and 3 micro g/mouse] 5min pre-test could not alter the memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 [1micro g/ mouse], pre-test intra-CA1 administration of L-arginine [1 and 3 micro g/ mouse], 24hr after training restored memory retrieval. Furthermore, in the animals under influence of post-training administration of WIN55, 212-2 [1 micro g/mouse], pre-test co-administration of non-effective doses of WIN55, 212-2 and L-arginine, increased the restoration of memory by the pre-test WIN55, 212-2. The findings of the present study suggest that NO system of dorsal hippocampus may play an important role in WIN55,212-2-induced amnesia and WIN55,212-2 state-dependent memory