Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6

Abstract

Brain areas expressing c-fos messenger RNA were mapped by quantitative in situ hybridization after 1-2 h of intoxication with 10 μg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, including the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus, locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NOstimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamic n. failed to induce penile erection, arguing against CNS involvement in this particular effect.

From the PnTx2-6 Toxin to the PnPP-19 Engineered Peptide: Therapeutic Potential in Erectile Dysfunction, Nociception, and Glaucoma

“…But only small amounts were observed in the brain and testicles compared to the penis ( Nunes et al, 2010 ). Corroborating this data, iodinated PnTx2-6 injected intraperitoneally in mice penetrates the BBB reaching brain areas associated with sexual function, as demonstrated by an increased activation of c-fos, an indirect marker for neuronal activity, in the paraventricular and stria terminalis nucleus ( Troncone et al, 2011 ). The major excitatory neurotransmitter in the brain, Glutamate, has a large array of normal physiological functions, including facilitating penile erection by acting in several areas, especially glutamatergic neurons in the hypothalamus.…”

Mapeamento da atividade cerebral de ratos submetidos aos estresses físico, psicológico e misto empregando [14C]-2-Deoxi-Glicose e expressão da proteína Fos

“…Dentre os diversos mediadores, mecanismos e sistemas propostos como importantes no TDM podem ser citados o desequilíbrio da transmissão monoaminérgica (SIEVER; DAVIS, 1985), receptores beta-adrenérgicos (FRAZER et al, 1982;TRONCONE;TUFIK, 1991), receptores alfa-2 adrenérgicos (GARCÍA-SEVILLA et al, 1999;NEUMEISTER et al, 2006), receptores alfa-1 adrenérgicos (STONE et al, 2007; GOLD; MACHADO-VIEIRA; PAVLATOU, 2015) os sistemas dopaminérgicos (BROWN et al, 1993;CABIB;PUGLISI-ALLEGRA, 1996), eixo HPA e corticosteróides (ASNIS et al, 1985;THOERINGER et al, 2007), citocinas (HAYLEY et al, 2005) SCHENE, 2007;COWEN, 2008), sugerindo que as monoaminas exerçam apenas uma influência modulatória na sintomatologia da depressão.…”

“…Todos esses fármacos mostravam-se ativos em modelos animais de depressão empregados pelos fabricantes. Assim, os estudos deste laboratório avaliaram a capacidade destes em bloquear a resposta de secreção de ACTH em três modelos de estresse.Esses trabalhos mostraram pela primeira vez que a supressão da secreção do ACTH por uma ou outra classe de antagonistas depende da natureza do estresse envolvido, de tal forma que apenas o uso concomitante de ambos os antagonistas leva a uma supressão total da resposta hipotalâmica ao estresseTRONCONE;TUFIK, 2007). Este procedimento foi, então, empregado para avaliar se a supressão total da resposta hipotalâmica poderia ter um efeito antidepressivo maior que o obtido com os fármacos individuais.…”