Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6
Lanfranco R P Troncone1, Katherine G Ravelli, Fabio C Magnoli
1Laboratory of Pharmacology, Instituto Butantan, São Paulo, Brazil. ltroncone@butantan.gov.br
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.
Insights
Spider toxin Tx2-6 activates numerous brain regions, including those linked to erectile function. However, direct brainstem injections did not cause erections, suggesting limited central nervous system involvement.
Area of Science:
- Neuroscience
- Toxicology
Background:
- The venom of the spider Phoneutria nigriventer contains toxins that affect the nervous system.
- Understanding the central effects of these toxins is crucial for neuropharmacology.
Purpose of the Study:
- To map the brain regions activated by Tx2-6, a toxin from Phoneutria nigriventer venom.
- To investigate the potential role of central nitric oxide (NO) and central nervous system (CNS) involvement in the toxin's effects.
Main Methods:
- Quantitative in situ hybridization was used to measure c-fos messenger RNA expression in rat brains.
- Animals were intoxicated with 10 μg/kg of Tx2-6 or saline.
Main Results:
- Tx2-6 caused significant c-fos activation in multiple brain areas, including the hypothalamus, thalamus, and brainstem nuclei.
- Specific areas like the paraventricular thalamic nuclei and bed nucleus of the stria terminalis showed selective activation.
- Direct injection of Tx2-6 into the paraventricular hypothalamic nucleus did not induce penile erection.
Conclusions:
- Tx2-6 broadly activates CNS areas, some overlapping with acute stress and NO-stimulated pathways.
- Despite activating brain regions implicated in erectile function, Tx2-6 does not appear to directly mediate penile erection via the central nervous system.
