Glyphosate, AMPA and glyphosate-based herbicide exposure leads to GFAP, PCNA and caspase-3 increased immunoreactive area on male offspring rat hypothalamus.

Glyphosate, aminomethylphosphonic acid (AMPA), and glyphosate-based herbicides altered the neuroendocrine axis, the content of brain neurotransmitters, and behavior in experimental animal models. Glyphosate alone, AMPA or Roundup® Active were administered to postpartum female rats, from P0 to P10, and their water consumption was measured daily. The immunoreactivity for glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA) and caspase-3 was measured in the anterior, medial preoptic, periventricular, supraoptic and lateroanterior hypothalamic nuclei of P0-P10 male pups after exposure, via lactation, to these xenobiotics. Puppies exposed to glyphosate had a moderate level of GFAP with no overlapping astrocyte processes, but this overlapping was observed after Roundup® Active or AMPA exposure. After being exposed to Roundup® Active or AMPA, PCNA-positive cells with strong immunoreactivity were found in some hypothalamic nuclei. Cells containing caspase-3 were found in all hypothalamic nuclei studied, but the labeling was stronger after Roundup® Active or AMPA exposure. Xenobiotics significantly increased the immunoreactivity area for all of the markers studied in the majority of cases (p<0.05). AMPA or Roundup® Active treated animals had a greater area of PCNA immunoreactivity than control or glyphosate alone treated animals (p<0.05). The effects observed after xenobiotic exposure were not due to increased water intake. The increased immunoreactivity areas observed for the markers studied suggest that xenobiotics induced a neuro-inflammatory response, implying increased cell proliferation, glial activation, and induction of apoptotic pathways. The findings also show that glyphosate metabolites/adjuvants and/or surfactants present in glyphosate commercial formulations had a greater effect than glyphosate alone. In summary, glyphosate, AMPA, and glyphosate-based herbicides altered GFAP, caspase-3, and PCNA expression in the rat hypothalamus, altering the neuroendocrine axis.

Mapping of folic acid in the children brainstem.

Using highly specific antisera, the neuroanatomical distribution of folic acid (FA) and retinoic acid (RA) has been studied for the first time in the children brainstem. Neither immunoreactive structures containing RA nor immunoreactive fibers containing FA were found. FA-immunoreactive perikarya (fusiform, small/medium in size, one short dendrite) were only found in the pons in three regions: central gray, reticular formation, and locus coeruleus. The number of cell bodies decreased with age. In the first case studied (2 years), a moderate density of cell bodies was observed in the central gray and reticular formation, whereas a low density was found in the locus coeruleus. In the second case (6 years), a low density of these perikarya was observed in the central gray, reticular formation, and locus coeruleus. In the third case (7 years), a low density of FA-immunoreactive cell bodies was found in the central gray and reticular formation, whereas in the locus coeruleus no immunoreactive cell bodies were observed. The distribution of FA in the central nervous system of humans and monkeys is different and, in addition, in these species the vitamin was located in different parts of the nerve cells. The restricted distribution of FA suggests that the vitamin is involved in specific physiological mechanisms.

Enkephalins and ACTH in the mammalian nervous system.

The pentapeptides methionine-enkephalin and leucine-enkephalin belong to the opioid family of peptides, and the non-opiate peptide adrenocorticotropin hormone (ACTH) to the melanocortin peptide family. Enkephalins/ACTH are derived from pro-enkephalin, pro-dynorphin or pro-opiomelanocortin precursors and, via opioid and melanocortin receptors, are responsible for many biological activities. Enkephalins exhibit the highest affinity for the δ receptor, followed by the µ and κ receptors, whereas ACTH binds to the five subtypes of melanocortin receptor, and is the only member of the melanocortin family of peptides that binds to the melanocortin-receptor 2 (ACTH receptor). Enkephalins/ACTH and their receptors exhibit a widespread anatomical distribution. Enkephalins are involved in analgesia, angiogenesis, blood pressure, embryonic development, emotional behavior, feeding, hypoxia, limbic system modulation, neuroprotection, peristalsis, and wound repair; as well as in hepatoprotective, motor, neuroendocrine and respiratory mechanisms. ACTH plays a role in acetylcholine release, aggressive behavior, blood pressure, bone maintenance, hyperalgesia, feeding, fever, grooming, learning, lipolysis, memory, nerve injury repair, neuroprotection, sexual behavior, sleep, social behavior, tissue growth and stimulates the synthesis and secretion of glucocorticoids. Enkephalins/ACTH are also involved in many pathologies. Enkephalins are implicated in alcoholism, cancer, colitis, depression, heart failure, Huntington's disease, influenza A virus infection, ischemia, multiple sclerosis, and stress. ACTH plays a role in Addison's disease, alcoholism, cancer, Cushing's disease, dermatitis, encephalitis, epilepsy, Graves' disease, Guillain-Barré syndrome, multiple sclerosis, podocytopathies, and stress. In this review, we provide an updated description of the enkephalinergic and ACTH systems.

Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem.

An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

Neuropéptidos en el encéfalo humano / Neuropeptides in the human brain

Resumen: los estudios en el encéfalo humano se han realizado con el fin de responder a varias preguntas de carácter científico relacionados con la neuroanatomía, neurofisiología, neurofarmacología,la neurología y la conducta. El encéfalo es el órgano en el que se encuentra la regulación de los reflejos y los mecanismos inconscientes como la transmisión del dolor, los cardiovasculares, los respiratorios, entre otros. Estos mecanismos están mediados por sustancias químicas tales como los neuropéptidos, que son cadenas cortas de aminoácidos que se han encontrado ampliamente distribuidos en el sistema nervioso central y periférico, además de ejercer acciones fisiológicas actuando como neurotransmisores, neuromoduladores (acciones paracrinas y autocrinas) y neurohormonas.En los últimos treinta años se ha incrementado el conocimiento sobre la distribución y función de los neuropéptidos en el sistema nervioso central de mamíferos (ratas, gatos, perros, alpacas, primates y humanos). Así, el objetivo de esta revisión se dirige a describir los datos más relevantes disponibles sobre los neuropéptidos en el encéfalo humano. Para ello se revisan aspectosimportantes de los neuropéptidos en el encéfalo humano como: a) La distribución, b) Las relaciones anatómicas, c) Las funciones fisiológicas, d) La coexistencia, y e) Las investigaciones futuras a realizar.

Abstract: the human brain has been used in laboratory as an experimental model in order to answer several scientific questions related to neuroanatomy, neurophysiology, neuropharmacology, neurology and behavior. The brain is the organ in which the regulation of reflexes and ®unconscious¼ mechanisms(transmission of pain, cardiovascular, respiratory, etc.) are carried out. These mechanisms are mediated by chemicals such as neuropeptides, which are shorter chains of amino acids that have been showed widely distributed in the central and peripheral nervous system and to exert physiologicalactions acting as neurotransmitters, neuromodulators (paracrine action and autocrine) and neurohormones.In the last thirty years, it has increased the knowledge on the distribution and function of neuropeptides in the central nervous system of mammals (rats, cats, dogs, alpaca, primates, and humans). Thus, the aim of this paper is to describe the most relevant information available about neuropeptides in the human brain. To do so will raise issues about neuropeptides in the human brain as: a) The distribution; b) The anatomical relationship; c) The physiological functions; d) The coexistence;and e) The related future research to make.