Coexistence of Intestinal Trefoil Factor (hITF) and Oxytocin in Magnocellular Neurons in the Human Hypothalamus

Abstract

Human intestinal trefoil factor hITF, a polypeptide of the P-domain family, was found to occur in hypothalamic neurons. With combined immunofluorescence and immunoperoxidase technique we investigated the coexistence of hITF with the neurohypophysial peptide oxytocin and the associated neurophysin I in sections of the human hypothalamus. In the supraoptic nucleus, 39.2% of magnocellular oxytocinergic perikarya show hITF immunoreactivity. A similar distribution was observed in perivascular hypothalamic oxytocinergic neurons, whereas in the paraventricular nucleus, 99% of the oxytocinergic neurons show hITF coexpression. In the periventricular nucleus (PEV), single, scattered neurons with both immunoreactivities occur. Our findings indicate that hITF and oxytocin are coexpressed in a portion of the magnocellular neurons in the human hypothalamus, and that hITF is among the neurohypophysial peptides.

PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

“…Neuropeptide trefoil factors (TFFs) are major secretory products of mucin-producing cells and can be synthesized in the brain (Griepentrog et al, 2000). Three types of TFFs have been characterized in mammals and humans: TFF1 (also designated pS2), TFF2 (hSP), and trefoil factor 3 (TFF3) (hP1.B/hITF).…”

“…TFF3 administration induced Fos protein expression in magnocellular oxytocin neurons in the hypothalamus (Derbyshire and Ludwig, 2004). TFF3 was found to colocalize with oxytocin in the paraventricular nuclei of the hypothalamus, suggesting similar roles for TFF3 and oxytocin (Griepentrog et al, 2000;Jagla et al, 2000). However, few studies have examined the role of TFF3 in the regulation of mood-related disorders.…”

mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine

“…The trefoil factor family (TFFs) peptides are major secretory products of mucin–producing cells and can be synthesized in the brain 11 . Three TFF peptides have been characterized in mammals, including humans: TFF1 (formerly designated pS2), TFF2 (formerly hSP), and TFF3 (also designated hP1.B/hITF).…”

“…In the central nervous system (CNS), TFF3 is mainly expressed in neuron and oligodendroglia of the hypothalamus, amygdala, hippocampus and prefrontal cortex (PFC) 11 17 18 . However, the role of TFF3 in the CNS is still not well understood.…”

Differential regional and cellular distribution of TFF3 peptide in the human brain

“…Moreover, molecular variants of the TFF3 gene and/or its altered expression in peripheral tissues have been linked with neurodegenerative and neuropsychiatric disorders (Alzheimer disease, Paterson et al 2014; Parkinson's disease: Kriks et al 2011;schizophrenia, Chissoe St et al 2008;Gardiner et al 2013;alcoholism, Hashimoto et al 2011). While local synthesis of TFF3 has unambiguously been demonstrated in oxytocin-producing neurons situated in the paraventricular and supraoptic hypothalamic nuclei (Probst et al 1995(Probst et al , 1996Griepentrog et al 2000;Jagla et al 2000;Schwarz et al 2001) as well as in neurons of the rodent cerebellar internal granular layer (Fu et al 2014), there is yet no consensus regarding the possible occurrence of TFF3 peptide in other brain regions. Remarkably, there are numerous reports on the presence of low to moderate TFF3 mRNA concentrations in most (if not all) brain areas of developing and adult murine and human brain and spinal cord (Probst et al 1995(Probst et al , 1996Reymond et al 2002;Hinz et al 2004;Cui et al 2006;Pereira et al 2009;Cadet et al 2010;Kriks et al 2011;Hashimoto et al 2011;Fu et al 2014; Allen Brain Atlas, http:// human.brain-map.org/microarray/gene/show/6991?rw=t; GeneNetwork, http://www.genenetwork.org/webqtl/ WebQTL.py?cmd=search&gene=Tff3; GeneCards, http:// www.genecards.org/cgi-bin/carddisp.pl?gene=TFF3).…”