International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2013.430.441F. El-OrabiNaglaa H. Abd-ElkaderOmar D. SchwartzDean 7201397Exertional heat injury represents a major risk for people working or exercising in hot environments. Currently, no pharmacological therapies are available and little is known about the molecular response to heat stress in the brain. This study examined changes in gene expression associated with hyperthermia in the hippocampus of pigs. Twelve pigs were kept at either 70°F (control) or 90°F (heat stressed) for 4, 8, 12 and 24 h. The heart rate, respiratory rate and body temperature of the pigs were monitored hourly. At 4, 8, 12 and 24 h, the hippocampus was excised from three pigs in each group and total RNA was obtained for use in differential display PCR. A total of 31 differentially expressed cDNAs were isolated. Differential expressions of eight genes were further confirmed by real-time PCR analysis. Only slight increases in the expression HSP70, HSP90 and HSP27 genes were reported after heat stress at all time points. After 12 h of heat stress, DNA polymerase ε p12 gene expression was stimulated to 2.55-fold of control level while it was down-regulated after both 4 and 8 h of heat stress exposure. Two genes encoding proteasome 26S subunits, PSMD10 and PSMB9, were also induced after exposure to heat stress for 4, 8 and 12 h to 2-fold or more of control levels. After 24 h, only PSMD10 was still elevated significantly. The superoxid dismutase-1 gene was significantly inhibited after both 8 and 12 h of heat stress, 0.39 and 0.45 fold of control levels respectively. The sodium-channel voltage gated β1 subunit gene was inhibited after heat stress. This inhibition was only significant after 24 h. In conclusion, most of the hippocampal genes of which the expression is altered by heat stress are play a role in cellular protection versus hyperthermic insult and some of the altered genes may play a role in heat-related brain pathogenesis. A greater understanding of heat-induced molecular changes in the brain could facilitate development of effective therapeutical strategies for treatment of heat-related illness.]]>Alm, P., H.S. Sharma, P.O. Sjoquist and J. Westman,200019383394Ardley, H.C., C.C. Hung and P.A. Robinson,2005579571576Atha, W.F.,20133110971108Awasthi, N. and B.J. Wagner,20054620822091Basu, R.,200984052Bechtold, D.A. and I.R. Brown,20032811631173Bergeron, M., C. Devore and S. Rice,201128e741e747Berman, A.,20058313771384Borges, J.C. and C.H. Ramos,200512257261Bose, S., F.L.L. Stratford, K.I. Broadfoot, G.G.F. Mason and A.J. Rivett,2004378177184Bouchama, A. and J.P. Knochel,20022519781988Cabelof, D.C., J.J. Raffoul, S. Yanamadala, Z. Guo and A.R. Heydari,2002in vivo.]]>2314191425Chaudhuri, A. and P.O. Behan,2004In vivo magnetic resonance spectroscopy in chronic fatigue syndrome.]]>71181183Chen, Y., A.P. Arrigo and R.W. Currie,2004287H1104H1114Chia, S.E. and K.J. Teo,200325503508Chou, Y.T., S.T. Lai, C.C. Lee and M.T. Lin,200319388393Coris, E.E., A.M. Ramirez and D.J. van Durme,200434916Fountoulakis, M., G.T. Tsangaris, A. Maris and G. Lubec,2005819115129Franklin, T.B., A.M. Krueger-Naug, D.B. Clarke, A.P. Arrigo and R.W. Currie,200521379392Friant, S., K.D. Meier and H. Riezman,20032237833791Fulda, S., A.M. Gorman, O. Hori and A. Samali,20102010Fung, M.L.,2000+ channels in hypoxia-induced neuronal injuries.]]>27569574Garrido, C., S. Gurbuxani, L. Ravagnan and G. Kroemer,2001286433442Gaughan, J.B., T.L. Mader, S.M. Holt and A. Lisle,200886226234Ghosh, B., C.D. Hanevold, K. Dobashi, J.K. Orak and I. Singh,199621533540Ghosh, G., K. De, S. Maity, D. Bandyopadhyay, S. Bhattacharya, R.J. Reiter and A. Bandyopadhyay,2007427182Gupta, M., S. Kumar, S.S. Dangi and B.L. Jangir,201332738Hermesh, H., R. Shiloh, Y. Epstein, H. Manaim, A. Weizman and H. Munitz,200015713271329Hosakote, Y.M., P.D. Jantzi, D.L. Esham, H. Spratt, A. Kurosky, A. Casola and R.P. Garofalo,201118315501560Huynh, T.T.T., A.J.A. Aarnink, M.W.A. Verstegen, W.J.J. Gerrits, M.J.W. Heetkamp, B. Kemp and T.T. Canh,20058313851396Janus, P., M. Pakuła-Cis, M. Kalinowska-Herok, N. Kashchak and K. Szołtysek et al.,20111611681175Kaarniranta, K., N. Oksala, H.M. Karjalainen, T. Suuronen and L. Sistonen et al.,2002101136140Khosla, R. and K.K. Guntupalli,199915251263Kitamura, C., T. Nishihara, Y. Ueno, K.K. Chen, T. Morotomi and J. Yano et al.,200699797806Kysely, J.,2004499197Lan, J., W. Li, F. Zhang, F.Y. Sun, T. Nagayama, C. O'Horo and J. Chen,20032313241339Le Grevès, P., H.S. Sharma, J. Westman, P. Alm and F. Nyberg,199770275278Lee, B.P.L., W.J. Rushlow, C. Chakraborty and P.K. Lala,200194674684Li, H., Y. Gu, Y. Zhang, M.J. Lucas and Y. Wang,2004in vitro.]]>117581Liang, P., W. Zhu, X. Zhang, Z. Guo and R.P. O'Connell et al.,19942257635764Lim, M.C., S.M. Brooke and R.M. Sapolsky,200361183188Lu, X.C., A.J. Williams, C. Yao, R. Berti and J.A. Hartings et al.,200477843857Lugo-Amador, N.M., T. Rothenhaus and P. Moyer,200422315327Marcuccilli, C.J., S.K. Mathur, R.I. Morimoto and R.J. Miller,199616478485Maroni, P., P. Bendinelli, L. Tiberio, F. Rovetta, R. Piccoletti and L. Schiaffonati,2003In vivo heat-shock response in the brain: Signalling pathway and transcription factor activation.]]>1199099Martin, R., G. Fitzl, C. Mozet, H. Martin, K. Welt and E. Wieland,20023714811487McEwen, B.S. and P.J. Gianaros,20101186190222Meiners, S., D. Heyken, A. Weller, A. Ludwig, K. Stangl, P.M. Kloetzel and E. Kruger,20032782151721525Milani, P., S. Gagliardi, E. Cova and C. Cereda,20112011Mountjoy, M., J.M. Alonso, M.F. Bergeron, J. Dvorak, S. Miller and S. Migliorini,201246800804Niakao, C., T. Ookawara, T. Kizaki, K. Suzuki, S. Haga, Y. Sato and H. Ohno,19991064761Niu, K.C., K.C. Lin, C.Y. Yang and M.T. Lin,200330745751Obrenovitch, T.P.,1998+-channel down-modulation versus presynaptic glutamate release inhibition.]]>9203212Oishi, K. and K. Machida,200262115121Pandita, T.K., R. Higashikubo and C.R. Hunt,20043591592Pavlik, A., I.S. Aneja, J. Lexa and B.A. Al-Zoabi,2003973179189Peluffo, H., L. Acarin, M. Faiz, B. Castellano and B. Gonzalez,20052005Perez-Crespo, M., M.A. Ramirez, R. Fernandez-Gonzalez, D. Rizos, P. Lonergan, B. Pintado and A. Gutierrez-Adan,200572502510Piccinini, M., M. Mostert, S. Croce, S. Baldovino, M. Papotti and M.T. Rinaudo,2003135135140Pospiech, H. and J.E. Syvaoja,2003387104Prapurna, D.R. and K.S. Rao,1997156773Qin, N., M.R. D'Andrea, M.L. Lubin, N. Shafaee, E.E. Codd and A.M. Correa,20031B subunit, a novel splicing variant of the β1 subunit.]]>27047624770Raji, N.S., T. Hari Krishna and K.S. Rao,200220491496Rattan, S.I.,20041019554558Rawal, A.K., M.G. Muddeshwar and S.K. Biswas,2004Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation.]]>2004Reynolds, L.P. and G.V. Allen,20032171177Rojo, A., M. Salinas, D. Martin, R. Perona and A. Cuadrado,20042473247334Rusyn, I., S. Asakura, B. Pachkowski, B.U. Bradford and M.F. Denissenko et al.,2004in vivo detection of chemical-induced chronic oxidative stress identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators.]]>6410501057Sakuraba, H., H. Mizukami, N. Yagihashi, R. Wada, C. Hanyu and S. Yagihashi,2002458596Segui, J., M. Gironella, M. Sans, S. Granell and F. Gil et al.,200476537544Sharma, H.S., J. Westman, F. Nyberg, C. Zimmer, J. Cervos-Navarro and P.K. Dey,19941994pp: 267-272pp: 267-272Sharma, H.S. and P.J. Hoopes,200319325354Sharma, H.S., K. Drieu, P. Alm and J. Westman,2000768186Sherman, M.Y. and A.L. Goldberg,2001291532Sonna, L.A., J. Fujita, S.L. Gaffin and C.M. Lilly,20029217251742Steinau, M., E.R. Unger, S.D. Vernon, J.F. Jones and M.S. Rajeevan,200482750755Takahashi, N., S. Kikuchi, Y. Dai, K. Kobayashi, T. Fukuoka and K. Noguchi,2003121441450Takahashi, Y., S.I. Moriwaki, Y. Sugiyama, Y. Endo and K. Yamazaki et al.,2005124435442Vandesompele, J., K. De Preter, F. Pattyn, B. Poppe, N. van Roy, A. De Paepe and F. Speleman,20022002Yao, S., M. Peng, X. Zhu, M. Cheng and X. Qi,200711715511564Yin, Y.H., N. Ahmad and M. Makmor-Bakry,20131611191132Zhao, Q.L., Y. Fujiwara and T. Kondo,20064011311143