Altered neurotrophic factors' expression profiles in the nucleus of the solitary tract of spontaneously hypertensive rats.
OBJECTIVE
Our previous findings suggest that the nucleus of the solitary tract (NTS), a pivotal region for regulating the set point of arterial pressure, exhibits abnormal inflammation in pre-hypertensive and spontaneously hypertensive rats (SHRs), with elevated anti-apoptotic and low apoptotic factor levels compared with that of normotensive Wistar-Kyoto (WKY) rats. Whether this chronic condition affects neuronal growth and plasticity in the NTS remains unknown. To unveil the characteristics of the neurodevelopmental environment in the NTS of SHRs, we investigated the expression of neurotrophic factors transcripts in SHRs.


METHODS
RT(2) Profiler PCR Array targeting rat neurotrophins and their receptors was used to screen for differentially expressed transcripts in the NTS of SHRs compared to that of WKY rats. Protein expression and physiological functions of some of the differentially expressed transcripts were also studied.


RESULTS
Gene and protein expressions of glial cell line-derived neurotrophic factor family receptor alpha-3 (Gfrα-3) factor were both upregulated in the NTS of adult SHRs. Gene expressions of corticotropin-releasing hormone-binding protein (Crhbp), interleukin-10 receptor alpha (Il-10ra) and hypocretin (Hcrt) were downregulated in the NTS of adult SHRs. The Gfrα-3 transcript was increased and the Hcrt transcript was decreased in the NTS of young pre-hypertensive SHRs, suggesting that these profiles are not secondary to hypertension. Moreover, microinjection in the NTS of hypocretin-1 decreased blood pressure in adult SHRs.


CONCLUSIONS
These results suggest that altered neurotrophic factors transcript profiles may affect the normal development and function of neuronal circuitry that regulates cardiovascular autonomic activity, thereby resulting in manifestations of neurogenic hypertension in SHRs.
Department of Biology, Faculty of Science, Ochanomizu University, Tokyo, Japan.
S S
SS
Gouraud
Department of Physiology, Wakayama Medical University, Wakayama, Japan.
M
M
Takagishi
Department of Physiology, Wakayama Medical University, Wakayama, Japan.
A
A
Kohsaka
Department of Physiology, Wakayama Medical University, Wakayama, Japan.
M
M
Maeda
Graduate School of Sport and Health Science, Juntendo University, Chiba, Japan.
H
H
Waki
D000818:Animals; D015153:Blotting, Western; D059014:High-Throughput Nucleotide Sequencing; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000378:metabolism*; D059467:Transcriptome
D009414:Nerve Growth Factors
hypertension; neurotrophic factors; nucleus of solitary tract