Breve introducción a la neuroinmunología / Brief introduction to the neuroimmunology

A partir de la década de los setentas se ha demostrado una importante dependencia direccional entre los sistemas inmune (SI) y el sistema nervioso central (SNC), con la intervención de mensajeros comunes. Las citocinas del SI son capaces de modular respuestas y procesos a nivel del SNC, mientras que los neurotransmisores y neuropéptidos pueden a su vez ejercer su efecto sobre grupos celulares especificos del SNC. Un grupo importante de estos péptidos es el de los opioides endógenos, como las endorfinas y las encefalinas. Las endorfinas alfa y beta tienen la capacidad de activar la quimiotaxis e influenciar la diferenciación y proliferación de linfocitos T y B. La ß-endorfina incrementa la actividad de las células natural killer (NK). La met-encefalina y la leu-encefalina desarrollan funciones de tipo inmunomodulador con respecto a la producción de anticuerpos (Acs) por las células plasmáticas. Incrementan la producción de Acs., pueden aumentar el número de leucocitos circulantes y la producción de interleucina-2 (IL-2). Una vía en el sistema neuroinmunológico es controlada por el eje-HPA (hipotálamo-pituitaria-adrenales, principal coordinador y regulador de las interacciones entre el sistema inmune, el SNC y el endocrino

Enkephalinergic mechanisms in midbrain (dPAG) in modulation of hypothalamically-induced predatory attack behaviour.

Present study was carried out in nine cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of lateral hypothalamus at a mean current strength of 690 microA. The attack was accompanied by minimal affective display and culminated in neck biting. Microinjections of delta-alanine methionine enkephaline (DAME) in 250 ng dose in dorsal periaqueductal gray completely suppressed the predatory attack. There was a significant increase in the threshold current strength for affective display components while the somatic components were completely inhibited even when the current strength was increased to 1000 microA. Microinjections of naloxone, an opioid antagonist in 1 microgram dose reversed the DAME blocking effect and the thresholds returned to control levels within 10 min of microinjections. Microinjections of naloxone alone in similar dose facilitated the response as indicated by a decrease in threshold current strengths for both affective display and somatomotor components. Control injections of saline in similar volumes (0.5 microliter) failed to produce any change. These findings indicate that hypothalamically induced predatory attack is inhibited by enkephalinergic mechanisms operating at the dPAG level in the midbrain.

Role of midbrain ventro-lateral tegmental area (VTA) enkephalinergic mechanisms in the facilitation of hypothalamically-induced predatory attack behaviour.

Bipolar concentric electrodes were implanted in five cats in extreme lateral regions of hypothalamus. These sites were electrically stimulated using biphasic square wave pulses at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized but live rat. At lower current strength (300 microA) only alertness with pupillary dilatation was produced. Gradual increase in the current strength led to the recruitment of somatic and affective components and a predatory attack was exhibited at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curves, which remained fairly constant when repeated over a period of 3-4 weeks. Bilateral microinjections of delta-alanine methoinine enkephaline (DAME) (500 ng in 0.5 microliter saline) in ventrolateral tegmental area (VTA) elevated the mean threshold current strength for affective components while somatomotor components were totally inhibited. The blocking effect of DAME persisted for 1 hour. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) also reversed the blocking effect of DAME and the thresholds returned to the control level within 10 min while microinjection of normal saline as control had no effect. The excitatory effects of naloxone and inhibitory effects of DAME were statistically significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates that enkephalinergic as well as opioidergic mechanisms operating at the midbrain (VTA) level are involved in the inhibition of predatory attack as elicited from lateral hypothalamus.