Table 1.
Preclinical endogenous neuropeptide measurement studies.
| Article title | First author & publication year |
Sample characteristics |
Substrates & measurement techniques | Relevant findings |
|---|---|---|---|---|
| “Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader–Willi syndrome” | Muscatelli et al. (2000) |
Necdin mouse model Age and sex: adult males Mutant: n = 4 Wild-type: n = 4 |
Substrate: OXT Collection location: hypothalamus (PVN) Technique: IHC |
-Significant decrease of 29% in the number of OXT-producing neurons were shown in lateral portion of the PVN in mutant mice compared to wild-type mice |
| “A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene” | Schaller et al. (2010) |
Magel2 mouse model Age and sex: neonatal males and females Mutant: n = 6–14 Wild-type: n = 5–14 |
Substrates: OXT and AVP Collection location: hypothalamus (PVN), pituitary gland Techniques: EIA; IHC |
-The number of OXT- and AVP- prohormone positive cells in the PVN was similar between mutant and wild-type mice. However, there was a 1.7-fold increase in the OXT-intermediate cells but not of AVP-intermediate cells in the PVN of mutant mice compared to wild-type mice -Significant reduction in OXT (36%) and AVP (20%) concentrations was found in the hypothalamus as a whole of mutant mice compared to wild-type mice -No significant difference was detected in the pituitary gland levels of OXT and AVP between mutant mice and wild-type mice |
| “An early postnatal oxytocin treatment prevents social and learning deficits in adult mice deficient for Magel2, a gene involved in Prader-Willi syndrome and autism” | Meziane et al. (2015) |
Magel2 mouse model Age and sex: adult males Mutant: n = 4–11 Wild-type: n = 4–10 |
Substrates: OXT, AVP, OXTR Collection location: anterior commissure to the posterior hypothalamus, hypothalamus (PVN), hypophysis, amygdala, lateral septum, dorsal vagal complex Techniques: EIA; mass spectroscopy; IHC; autoradiography |
-Significant increase in OXT (34%) and AVP (21%) concentrations was detected in hypophysis, whereas only AVP (%15) concentration was increased in the hypothalamus of mutant mice compared to wild type mice -Significant increase in the total number of OXT-positive neurons (26%) in the entire PVN but no accumulation of OXT-intermediate neurons was found despite the 22% more OXT-prohormone and -intermediate neurons in the rostral PVN in mutant mice compared to wild-type mice -Significant increases in OXT immunoreactivity were found in the medial amygdala (300%), the lateral septum (172%), and the dorsal vagal complex (33%) in mutant mice compared to wild-type mice -Significant decrease in OXTR density (26%) was detected in lateral septum of mutant mice compared to wild-type mice. |
| “Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance” | Ates et al. (2019) |
Magel2 mouse model Age and sex: adult (5–7 weeks old) males and females Mutant: n = 2–6 Wild-type: n = 2–7 |
Substrate: OXT Collection location: hypothalamus (PVN) Techniques: electrophysiology; confocal microscopy |
-Significant decrease in baseline firing rates and frequency of action potentials in OXT neurons in the PVN of mutant mice compared to wild-type mice -Significant selective reduction in excitatory drive and increase in inhibitory drive onto OXT neurons in the PVN of mutant mice compared to wild-type mice -No deficit in the number of spiny protrusions from basal OXT neuronal dendrites in the PVN of mutant mice compared to wild-type mice |
| “Colocalization of Oxtr with Prader-Willi syndrome transcripts in the trigeminal ganglion of neonatal mice” | Vaidyanathan et al. (2020) |
Magel2 mouse model Age and sex: neonatal males and females Mutant: n = 8 Wild-type: n = 12 |
Substrate: OXTR Collection location: trigeminal ganglion, lateral periodontium, rostral periodontium, tongue, olfactory epithelium, whisker pads and brainstem Techniques: chromogenic in situ hybridization; autoradiography |
-OXTR is co-expressed with Magel2 and other PWS gene transcripts in the trigeminal ganglion of wild-type mice -Trigeminal ganglion neurons express OXTR but not Magel2 in the mutant mice -Significant reduction in OXTR binding density in the lateral periodontia with intact levels in the rest of the head of mutant mice compared to wild-type mice |
| “Loss of MAGEL2 in Prader-Willi syndrome leads to decreased secretory granule and neuropeptide production” | Chen et al. (2020) |
Magel2 mouse model Age and sex: adult mice (sex unspecified) Mutant: n > 5 Wild-type: n = 5–6 |
Substrates: OXT, AVP Collection location: whole hypothalamus, plasma Techniques: Quantitative Proteomic/Mass Spectrometry, EIA |
-Significant reduction of OXT and AVP levels (~50%) in the hypothalamus of mutant mice compared to wild-type mice -Significant decrease in OXT and AVP concentrations in the plasma of mutant mice compared to wild-type mice |
| “Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model” | Borie et al. (2021) |
Magel2 mouse model Age and sex: adult males Mutant: n = 5–6 Wild-type: n = 5–6 |
Substrates: AVP, AVPR1A, AVPR1B and AVPR2 Collection location: lateral septum Techniques: IHC, autoradiography |
-Significant decrease in overall AVP receptor densities in the somatostatin neurons of the dorsal lateral septum in mutant mice compared to wild-type mice -Significant reduction in the number and length of AVP fibers in the dorsal lateral septum of mutant mice compared to wild-type mice |
AVP, arginine vasopressin; AVPR1A, arginine vasopressin receptor 1A; AVPR1B, arginine vasopressin receptor 1B; AVPR2, arginine vasopressin receptor 2; EIA, enzyme immunoassay; IHC, immunohistochemistry; OXT, oxytocin; OXTR, oxytocin receptor; PVN, paraventricular nucleus