Expression of Glutamate Receptors in the Medial Vestibular Nuclei following Acute Hypotension

Acute hypotension induced excitation of electrical activities and expression of c-Fos protein and pERK in the vestibular nuclei. In this study, to investigate the excitatory signaling pathway in the vestibular nuclei following acute hypotension, expression of NR2A and NR2B subunits of glutamate NMDA receptor and GluR1 subunit of glutamate AMPA receptor was determined by RT-PCR and Western blotting in the medial vestibular nucleus 30 min after acute hypotension in rats. Acute hypotension increased expression of NR2A, NR2B, and pGluR1 in the medial vestibular nuclei. These results suggest that both of NMDA and AMPA glutamate receptors take part in transmission of excitatory afferent signals following acute hypotension.

Role of the Peripheral Vestibular System on Neuroplasticity Induced by Hypergravity Stimulation

BACKGROUND AND OBJECTIVES: Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular system following an exposure to hypergravity stimulus was determined in rats. MATERIALS AND METHOD: The animals were subjected to 2 G force (two-fold earth's gravity) stimulus for 3 hours, and were examined at post-stimulus hours 0, 2, 6, 12, and 24. Real time reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze temporal changes in the expression of c-fos mRNA. RESULTS: The hypergravity stimulation produced the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, vestibulocerebellum, and vestibular cortex. The peak expression occurred at hour 6 in the animals hypergravity-stimulated for 3 hours. Bilateral labyrinthectomy significantly attenuated the degree of up-regulation in c-fos mRNA expression. MK-801, an NMDA receptor antagonist, also significantly attenuated the degree of up-regulation in c-fos mRNA expression. CONCLUSION: These results indicate that the adaptive neuroplasticity in response to an altered gravity occurs in the vestibular-related organs in the central nervous system, in which peripheral vestibular receptors and NMDA receptors play an important role.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

Extracellular regulated protein kinase1/2 (pERK1/2) is one of the major regulatory factors for transcription of the c-fos oncogene in neurons. The purpose of this study was to evaluate the expression of phosphorylated ERK1/2 within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following the acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2 in these nuclei occurred within 5 min after hemorrhage. However, in bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. Western blot confirmed the effect of bilateral labyrinthectomy on pERK1/2 protein expression in the medial vestibular nucleus 5 min after hemorrhage. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of ERK 1/2 in the VN.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

The purpose of the present study was to elucidate the possible involvement of the medial vestibular nucleus (MVN) and inferior vestibular nucleus (IVN) following acute hypotension in the vestibulo- autonomic reflex through vestibulosolitary or vestibuloventrolateral projections. Acute hypotension- induced cFos expression was assessed in combination with retrograde cholera toxin B subunit (CTb) tract tracing. After injection of CTb into the solitary region, CTb-labeled neurons were located prominently around the lateral borders of the caudal MVN and medial border of the IVN. The superior vestibular nucleus also had a scattered distribution of CTb-labeled neurons. After injection of CTb toxin into the unilateral VLM, the distributions of CTb-labeled neurons in the MVN and IVN were similar to that observed after injection into the solitary region, although there were fewer CTb-labeled neurons. In the caudal MVN, about 38% and 13% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. In the IVN, 14% and 7% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. Therefore, the present study suggests that acute arterial hypotension may result in activation of vestibulosolitary pathways that mediate behavioral and visceral reflexes, and vestibuloventrolateral medullary pathways that indirectly mediate vestibulosympathetic responses.

Effect of Ginkgo biloba on Expression of c-Fos Protein in the Vestibular Nuclear Complex following Unilateral Labyrinthectomy in Rats

BACKGROUND AND OBJECTIVES: The neuroprotective effect of Ginkgo biloba has been demonstrated in several in vivo and in vitro models. The effect of Ginkgo biloba on vestibular compensation following unilateral labyrinthectomy (UL) was investigated. Material and Methods: Spontaneous nystagmus and c-Fos protein expression were measured following UL in Sprague-Dawley rats with pretreatment of Ginkgo biloba (50 mg/kg, i.p.). RESULTS: After pretreatment with Ginkgo biloba (50 mg/kg, i.p.) expression of c-Fos protein in the vestibular nuclear complex and frequency of spontaneous nystagmus were measured till 24 hours after UL. UL produced spontaneous nystagmus with frequency of 124+/-.2 beats/min at post-op 2 hrs and 70+/-.1 beats/min at post-op 24 hrs. Pretreatment with Ginkgo biloba significantly decreased the frequency of spontaneous nystagmus till post-op 24 hrs compared to control group (p<0.05). UL produced marked expression of c-Fos protein in bilateral medial vestibular nucleus, inferior vestibular nucleus, and superior vestibular nucleus, and the number of expression was significantly higher in contralateral vestibular nuclei to the lesion than ipsilateral vestibular nuclei at post-op 2 hrs (p<0.01). The number of c-Fos protein expression was decreased with time and significantly higher in ipsilateral vestibular nuclei than contralateral ones at post-op 24 hrs (p<0.01). Pretreatment with Ginkgo biloba significantly decreased the number of c-Fos protein expression following UL (p<0.01) and abolished the asymmetry of c-Fos protein expression in bilateral vestibular nuclei at post-op 24 hrs. CONCLUSION: These results suggest that Ginkgo biloba may facilitate vestibular compensation following UL through modulation of neurotransmitters and neuroprotective effects.

Immunohistochemical Identification of Phosphorylated Extracellular Signal-Regulated Kinase1/2 in Rat Vestibular Nuclei by Unilateral Labyrinthectomy

This study evaluated the expression of phosphorylated signal-regulated kinase1/2 (pERK1/2), which is one of the main factors regulating transcription of the cfos oncogene in neurons, in the vestibular nuclei of Sprague-Dawley rats following unilateral labyrinthectomy (UL). Surgical UL was performed to eliminate afferent signals from the peripheral vestibular receptors in the inner ear, under a surgical microscope, 2 hours after anesthesia. Significant numbers of pERK1/2 immunoreactive neurons were seen in the superior, medial, and inferior vestibular nuclei. There were more pERK1/2 immunoreactive cells in the vestibular nuclei contralateral than in the vestibular nuclei ipsilateral to the injured labyrinth, which resulted in significant asymmetric expression of pERK1/2 immunoreactive cells. Subsequently, the pERK1/2 immunoreactivity decreased rapidly, disappearing 90 min after labyrinthectomy. No pERK1/2 labeling was seen in the lateral vestibular nucleus. These results suggest that intracellular signal pathways for the activation of extracellular signal-regulated kinase in the vestibular nuclei are involved in lesion-neural plasticity in the vestibular system

Effect of vestibular end-organs on expression of cFos and FosB injury in the hippocampal formation of rats

It is well known that the hippocampal formation requires primary vestibular sensory information to generate spatial memory during self motion in human. The purpose of the present study was to evaluate the effect of unilateral deafferentation of vestibular sensory information on cFos and FosB proteins, a family of immediate early gene-related proteins known as metabolic marker for neural excitation in the hippocampal formation of rats. Adult Sprague-Dawley rats weighing 250 - 300 g were surgically ablated of the peripheral vestibular system in the inner ear and sacrificed at 2, 6, 24, 48, 72 hours after surgical operation. Immunohistochemical staining and Western blot method were adapted to see change in expression of cFos and FosB proteins in the hippocampal formation. A significant change of Fos B immunoreactivity was observed in granular cell layer of the dentate gyrus, CA1 subfield of the hipocampus at 2 hours after unilateral labyrinthectomy. Thereafter, the number of FosB like immunoreactive neurons in these areas increased rapidly, peaked at 48 hours post operatively time. Western blot for FosB protein supported further time-dependent change of FosB revealed by immunohistochemical staining. In addition, granular cell layer showed more significant expression of FosB LI neurons in the caudal dentate gyrus than the rostral one. In contrast, moderate number of cFos LI neurons was detected in polymorphic cell layer of the dentate gyrus, pyramidal cell layer of CA1, and subiculum but not in granular cell layer of the dentate gyrus at 2 hours after labyrinthectomy. The number of cFos LI neurons in the hippocampal formation was rapidly decreased at 6 hours and then returned to basal value 24 hours after operation. These results suggest that unilateral ablation of the peripheral vestibular sensory information elicit spatio-temporal differences of cFos and FosB expressions in the hippocampal formation of rats.