Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocampus of Wistar rats.

This study focused on the effects of zinc oxide nanoparticles (nano-ZnO) on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM) was determined, and then long-term potentiation (LTP) and depotentiation were measured in the perforant pathway to dentate gyrus (DG) in anesthetized rats. The data showed that, (1) in MWM, the escape latency was prolonged in the nano-ZnO group and, (2) LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.

Impairments of behavior, information flow between thalamus and cortex, and prefrontal cortical synaptic plasticity in an animal model of depression.

Growing evidence suggests the involvement of stress in the pathophysiology of depression. This study was designed to test behavioral and electrophysiological changes in a stressed model of depression. Rats were randomly divided into control and stressed groups. Chronic unpredictable stress combined with isolation rearing was applied in rats of stressed group for three weeks. Weight and sucrose consumption were measured during the model establishing period. Behavior was measured by Morris water maze. Electroencephalography (EEG) of thalamus and prefrontal cortex was recorded after behavioral tests, followed by recording long-term potentiation (LTP) of the same thalamocortical pathway. Results showed that rats' weight and sucrose intake were significantly lower in stressed group than those in control group. In stressed group, escape latency of reversal training stage in water maze test was significantly prolonged, and platform crossings of reversal probe trials were significantly decreased. EEG test showed that the extent of thalamus driving prefrontal cortex was decreased in stressed group. LTP test showed lower postsynaptic potential amplitude in stressed group as compared to that in control group. In conclusion, chronic stress could cause certain behavioral changes in rats, with possible mechanism of impairing EEG of certain thalamocortical pathway and prefrontal cortical synaptic plasticity.

Heat stress preconditioning improves cognitive outcome after diffuse axonal injury in rats.

This study investigates the influence of heat stress preconditioning on cognitive outcome for rats with diffuse axonal injury (DAI), and attempts to examine the underlying mechanisms. Wistar rats were divided into four groups: rats subjected to heat stress preconditioning 24 h before induction of DAI (n = 10; HSDAI group), a DAI alone group (n = 10), a heat stress alone group (n = 10), and a sham-injury group (n = 10). From day 14 post-injury, the rats' learning abilities and memory were tested using the Morris water maze (MWM) task, followed by long-term potentiation (LTP) recording of the hippocampus. In addition, hematoxylin and eosin staining (H&E) and immunohistochemical staining (IHC) were conducted to determine the presence of brain lesions and expression of heat shock protein 70 (HSP70) at 24 h, and on days 14 and 20 post-injury. The rats in the DAI group displayed impaired MWM performance and attenuated LTP compared to the sham group (p < 0.05); the rats in the HSDAI and HS groups showed significant improvement in both MWM and LTP compared with the DAI group (p < 0.05), and no significant differences with the sham group (p > 0.05). Following injury, retraction balls, shrunken neurons, and HSP70 expression were visible in the brains of rats from the DAI and HSDAI groups; recovery was expedited in the rats belonging to the HSDAI group, as these pathological changes were alleviated, coincident with higher expression of HSP70. The rats' abilities for learning and memory were impaired following DAI; this may be due to the disconnection of brain regions, damage to neurons in the hippocampus, and a decrease in synaptic plasticity. Heat stress preconditioning is able to significantly attenuate this cognitive impairment, possibly mediated by the neuroprotective effect of HSP70.

Cardiac sympatho-excitatory action of PVN-spinal oxytocin neurones.

A significant proportion of the spinally projecting neurones in the paraventricular nucleus are immunoreactive for oxytocin. Some of these oxytocin neurones terminate on sympathetic preganglionic neurones in the upper thoracic spinal cord, a region from which cardiac sympathetic neurones originate. No studies have so far identified a cardiac action of the supraspinal oxytocin neurones. The present study was designed to test the hypothesis that these oxytocin neurones excite spinal cardiac sympathetic neurones. This was done by measuring heart rate changes in response to intrathecal oxytocin and a selective agonist, and to stimulation of paraventricular neurones before and during blockade of spinal sites with selective antagonists. Rats were anaesthetised with chloralose and urethane (50 mg and 650 mg/kg) and recordings were made of heart rate and blood pressure. Drugs in a volume of 10 microl were applied to the upper thoracic spinal cord via a catheter placed intrathecally with its tip at T2. The paraventricular nucleus was explored with a glass micropipette, placed stereotaxically, and filled with d,l-homocysteic acid (DLH, 200 mM) for exciting neurones and pontamine sky blue for marking the position. Oxytocin (0.002 mM) applied to the spinal cord elicited increases in heart rate (26+/-5 beats per minute). This was mimicked by a highly selective oxytocin agonist. These heart rate increases were blocked selectively by two different oxytocin antagonists but unaffected by a V(1a) vasopressin antagonist. Excitation of sites in dorsal and medial parvocellular sub-nuclei of the paraventricular nucleus elicited increases in heart rate (36+/-3 bpm) which were significantly reduced by oxytocin antagonists but not affected by V(1a) antagonist. Also these induced increases in heart rate were unaffected by vagotomy or i.v. atropine but were abolished by i.v. esmolol. It is concluded that there is a population of paraventricular-spinal oxytocin neurones that excite cardiac sympathetic preganglionic neurones controlling heart rate.

[Effect of Chinese medicine Huishen granule on cognitive outcome following diffuse axonal injury: experiment with rats].

OBJECTIVE: To investigate the influence of Chinese medicine Huishen granule (HG) containing ginseng, grassleaved sweet flag rhizome, pilose deer antler, etc, on learning and memory functions in diffuse axonal injury (DAI) and the mechanisms thereof. METHODS: Impact acceleration method was used to establish DAI Wistar rat models. Twenty model rats were randomly divided into 2 equal groups, the DAI+HG group treated with gastric perfusion of HG 3 times a day since 24 h after the establishment of model for 14 days, and the DAI group without treatment. Ten rats underwent sham operation as controls. Fourteen days after the injury, Morris water maze (MWM) test was used to detect the rat's abilities of learning and memory for continuous 5 days. The changes of escape latency in acquisition of the task, the percentage of time spent in target quadrant, and the number of crossing the point of original platform in probe test were recorded. At day 20 after the-operation, the rats were subjected to long-term potentiation (LTP) recording in hippocampus to measure the percentage of slope and baseline of excitatory post-synaptic potential (EPSP). Two rats from each group were killed 24 h, 14 d, and 20 d after the operation with their brains taken out, HE and immunohistochemical staining were employed to exam the brain lesion at 24 h, day 14 and 20 post-injury. RESULTS: The escape latency of the DAI group was (32.8+/-4.6) s, significantly longer than those of the DAI+HG and sham operation groups [(20.3+/-0.7) and (16.8+/-0.8) s respectively, both P<0.05]. The target quadrant staying time percentage and number of platform location crossings of the DAI group were (36.4+/-3.2)% and 4.5+/-0.6 respectively, both significantly less than those of the DAI+HG and sham operation groups [(46.0+/-2.4)% and 6.8+/-0.8, and (46.9+/-2.1)% and 8.1+/-0.8 respectively, all P<0.05]. The LTP level of the DAI group was (101.4+/-3.3)%, significantly lower than those of the DAI+HG and sham operation groups [(116.3+/-6.7)% and (117.9+/-2.8)% respectively, both P<0.05]. No significant differences in the parameters were found between the DAI+HG and sham operation groups (all P>0.05). Classical pathological changes of DAI occurred in the brains of the DAI and DAI+HG groups at the time point of 24 h, and mitigated partly at the time points of day 14 and 20. CONCLUSION: The learning and memory impairment of DAI was ameliorated significantly with the treatment of Chinese medicine HG, owing to the recuperation of synaptic plasticity in hippocampal area.