RESUMO
The premammillary nucleus (PMM) of the turkey mediobasal hypothalamus, where dopamine-melatonin (DA-Mel) neurons are localized, is a site for photoreception and photoperiodic time measurement, which is essential for the initiation of avian reproductive seasonality. In addition, this area could also be responsible for the onset and maintenance of photorefractoriness at the end of the breeding season due to the enhanced inhibitory effect of γ-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter in the central nervous system which interferes with the photosexual response in the turkey, a seasonally breeding bird. Here, we further characterized the GABAA receptor subunits in the PMM DA-Mel neurons related to reproductive seasonality and the onset of photorefractoriness. GABAA receptor subunits and GABA synthesis enzymes in the PMM of photosensitive and photorefractory turkey hens were identified using real-time qRT-PCR. The upregulation of GABAA receptor α1-3, ß2-3, γ1-3, ρ1-3, δ, and θ mRNA expression were observed in the PMM of photorefractory birds when compared to those of photosensitive ones while there is no change observed in the GABA synthesis enzymes, glutamate decarboxylase 1 and 2. Those upregulated GABAA receptor subunits were further examined using immunohistochemical staining and they appeared to be co-localized within the PMM DA-Mel neurons. The upregulation of GABAA receptor subunits observed in the PMM of photorefractory birds coincides with a lack of responsiveness to a light stimulus provided during the photosensitive phase. This is supported by the absence of c-fos induction and TH upregulation in the PMM and a subsequence inhibition of c-fos and GnRH-I expression in the nucleus commissurae pallii. The augmented GABAA receptor subunits expression may mediate an enhancement of inhibitory GABAergic neurotransmission and the subsequent interference with the photosexual response. This could contribute to the state of photorefractoriness and the termination of breeding activities in the turkey, a temperate zone bird.
Assuntos
Neurônios GABAérgicos/metabolismo , Hipotálamo Posterior/metabolismo , Hipotálamo Posterior/efeitos da radiação , Luz , Receptores de GABA-A/metabolismo , Perus/metabolismo , Regulação para Cima/efeitos da radiação , Animais , Arilalquilamina N-Acetiltransferase/metabolismo , Dopamina/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/genética , Melatonina/metabolismo , Fotoperíodo , Precursores de Proteínas/genética , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de GABA-A/química , Reprodução/fisiologia , Reprodução/efeitos da radiação , Estações do Ano , Transmissão Sináptica , Triptofano Hidroxilase/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
The field of neuromodulation is emerging as a promising and alternative therapeutical option for many drug-resistant clinical conditions, including painful syndromes such as refractory chronic cluster headache (CCH) and trigeminal neuralgia. We here report a series of patients who have undergone Deep Brain Stimulation (DBS) of Posterior Hypothalamus for chronic cluster headache, trigeminal neuralgia and atypical facial pain, matching their corresponding clinical results and also suggesting a role for Great Occipital Nerve Stimulation (which is a much less invasive procedure) in the treatment of CCH. According to us, the refinement of surgical techniques and of metabolic and functional brain neuroradiological investigations will lead to a refinement of the therapeutical strategies in such patients.
Assuntos
Cefaleia Histamínica/terapia , Estimulação Encefálica Profunda/métodos , Neuralgia do Trigêmeo/terapia , Seguimentos , Humanos , Hipotálamo Posterior/fisiopatologia , Hipotálamo Posterior/efeitos da radiação , Resultado do TratamentoRESUMO
The trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes characterised by intense pain and associated activation of cranial parasympathetic autonomic outflow pathways out of proportion to the pain. The TACs include cluster headache, paroxysmal hemicrania and SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing). The pathophysiology of these syndromes involves activation of the trigeminal-autonomic reflex, whose afferent limb projects into the trigeminocervical complex in the caudal brainstem and upper cervical spinal cord. Functional brain imaging has shown activations in the posterior hypothalamic grey matter in TACs. This paper reviews the anatomy and physiology of these conditions and the brain imaging findings. Current treatments are summarised and the role of neuromodulation procedures, such as occipital nerve stimulation and deep brain stimulation in the posterior hypothalamus are reviewed. Neuromodulatory procedures are a promising avenue for these highly disabled patients with treatment refractory TACs.