Papel de la eminencia talámica, el sistema olfativo principal y el sistema olfativo accesorio en la maduración sexual del encéfalo y las manifestaciones clínico-morfológicas del síndrome de Kallmann

El desarrollo de sistema olfativo y la diferenciación sexual del encéfalo, tanto en el hombre como en los animales, están estrechamente relacionados. Actualmente, se describe la imbricación entre la formación del sistema olfativo principal y la migración de las neuronas que sintetizan la hormona liberadora de gonadotrofinas (GnRF). Estas neuronas GnRF se desplazan por los nervios olfatorios, desde la parte medial del epitelio nasal al bulbo olfatorio, continúan por el encéfalo rostral hasta alcanzar el hipotálamo anterior. Por otro lado, el síndrome de Kallmann es un trastorno genético en el cual se combina el hipogonadismo hipogonadotrópico y la anosmia. El hipogonadismo se caracteriza por la ausencia o reducción de los niveles de hormona liberadora de gonadotrofinas y la anosmia la aplasia del bulbo olfatorio. En esta revisión se analizan las estructuras responsables de la maduración del sistema olfativo principal y accesorio, la diferenciación sexual del encéfalo y su relación con todas las manifestaciones clínicas y morfológicas del síndrome Kallmann. The olfactory system development and brain sexual maturation, in man and animals, are closely related. Currently the overlap between the formation of the olfactory system and the migration of neurons that synthesize gonadotropin-releasing hormone (GnRF) are described. The GnRF neurons migrate from the medial portion of the nasal epithelium through the olfactory nerves and the main olfactory bulb to the anterior hypothalamus. Furthermore, Kallmann syndrome (KS) is a genetic disorder in which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropin-releasing hormone and anosmia is due to aplasia of the olfactory bulb. The basic clinical manifestations of KS are: anosmia and the absence of puberty. The structures responsible for the maturation of the main and accessory olfactory systems, the sexual differentiation of the brain and its relationship with all the clinical manifestations of Kallmann syndrome are analyzed in this revie

Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease

Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Aβ42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Aβ transporters: the low density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin (TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Aβ burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Aβ) and diminished secretion of TTR (less neuroprotection against cortical Aβ toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD