Details der Publikation - Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism

Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism

Abstract The enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a pivotal role in the regulation of nitric oxide levels by degrading the main endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Growing evidence highlight the potential implication of DDAH/ADMA axis in the etiopathogenesis of several neuropsychiatric and neurological disorders, yet the underlying molecular mechanisms remain elusive. In this study, we sought to investigate the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance. To achieve this, a global DDAH1 knock-out (DDAH1-ko) mouse strain was employed. Behavioral testing and brain region-specific neurotransmitter profiling have been conducted to assess the effect of both genotype and sex. DDAH1-ko mice exhibited increased exploratory behavior toward novel objects, altered amphetamine response kinetics and decreased dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) level in the piriform cortex and striatum. Females of both genotypes showed the most robust amphetamine response. These results support the potential implication of the DDAH/ADMA pathway in central nervous system processes shaping the behavioral outcome. Yet, further experiments are required to complement the picture and define the specific brain-regions and mechanisms involved..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:130
Enthalten in:	Journal of neural transmission - 130(2023), 9 vom: 16. Feb., Seite 1097-1112

Sprache:	Englisch

Beteiligte Personen:	Kozlova, Alena A. [VerfasserIn] Rubets, Elena [VerfasserIn] Vareltzoglou, Magdalini R. [VerfasserIn] Jarzebska, Natalia [VerfasserIn] Ragavan, Vinitha N. [VerfasserIn] Chen, Yingjie [VerfasserIn] Martens-Lobenhoffer, Jens [VerfasserIn] Bode-Böger, Stefanie M. [VerfasserIn] Gainetdinov, Raul R. [VerfasserIn] Rodionov, Roman N. [VerfasserIn] Bernhardt, Nadine [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	Amphetamine Behaviour DDAH1 Dopamine Knock-out mice Nitric oxide

RVK:	RVK Klassifikation ELIB09 ELIB10 ELIB24

Anmerkungen:	© The Author(s) 2023

doi:	10.1007/s00702-023-02597-7

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2145246282

Internformat


LEADER	01000naa a22002652 4500
001	OLC2145246282
003	DE-627
005	20240118103521.0
007	cr uuu---uuuuu
008	240118s2023 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1007/s00702-023-02597-7 \|2 doi
035			\|a (DE-627)OLC2145246282
035			\|a (DE-He213)s00702-023-02597-7-e
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
082	0	4	\|a 610 \|q VZ
084			\|a ELIB09 \|q VZ \|2 rvk
084			\|a ELIB10 \|q VZ \|2 rvk
084			\|a ELIB24 \|q VZ \|2 rvk
100	1		\|a Kozlova, Alena A. \|e verfasserin \|0 (orcid)0000-0002-0254-6264 \|4 aut
245	1	0	\|a Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism
264		1	\|c 2023
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
500			\|a © The Author(s) 2023
520			\|a Abstract The enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a pivotal role in the regulation of nitric oxide levels by degrading the main endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Growing evidence highlight the potential implication of DDAH/ADMA axis in the etiopathogenesis of several neuropsychiatric and neurological disorders, yet the underlying molecular mechanisms remain elusive. In this study, we sought to investigate the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance. To achieve this, a global DDAH1 knock-out (DDAH1-ko) mouse strain was employed. Behavioral testing and brain region-specific neurotransmitter profiling have been conducted to assess the effect of both genotype and sex. DDAH1-ko mice exhibited increased exploratory behavior toward novel objects, altered amphetamine response kinetics and decreased dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) level in the piriform cortex and striatum. Females of both genotypes showed the most robust amphetamine response. These results support the potential implication of the DDAH/ADMA pathway in central nervous system processes shaping the behavioral outcome. Yet, further experiments are required to complement the picture and define the specific brain-regions and mechanisms involved.
650		4	\|a DDAH1
650		4	\|a Knock-out mice
650		4	\|a Behaviour
650		4	\|a Nitric oxide
650		4	\|a Dopamine
650		4	\|a Amphetamine
700	1		\|a Rubets, Elena \|4 aut
700	1		\|a Vareltzoglou, Magdalini R. \|0 (orcid)0000-0002-8226-0505 \|4 aut
700	1		\|a Jarzebska, Natalia \|4 aut
700	1		\|a Ragavan, Vinitha N. \|4 aut
700	1		\|a Chen, Yingjie \|4 aut
700	1		\|a Martens-Lobenhoffer, Jens \|4 aut
700	1		\|a Bode-Böger, Stefanie M. \|4 aut
700	1		\|a Gainetdinov, Raul R. \|0 (orcid)0000-0003-2951-6038 \|4 aut
700	1		\|a Rodionov, Roman N. \|0 (orcid)0000-0002-7470-7776 \|4 aut
700	1		\|a Bernhardt, Nadine \|0 (orcid)0000-0002-3188-8431 \|4 aut
773	0	8	\|i Enthalten in \|t Journal of neural transmission \|d Springer Vienna, 1950 \|g 130(2023), 9 vom: 16. Feb., Seite 1097-1112 \|h Online-Ressource \|w (DE-627)300185901 \|w (DE-600)1481655-6 \|w (DE-576)09450542X \|x 1435-1463 \|7 nnns
773	1	8	\|g volume:130 \|g year:2023 \|g number:9 \|g day:16 \|g month:02 \|g pages:1097-1112
856	4	0	\|u https://dx.doi.org/10.1007/s00702-023-02597-7 \|z kostenfrei \|3 Volltext
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_OLC
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_32
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_152
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_171
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_250
912			\|a GBV_ILN_267
912			\|a GBV_ILN_281
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_636
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2093
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2107
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2134
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2144
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2188
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2433
912			\|a GBV_ILN_2446
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2474
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_2548
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4046
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4246
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4328
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4336
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
936	r	v	\|a ELIB09
936	r	v	\|a ELIB10
936	r	v	\|a ELIB24
951			\|a AR
952			\|d 130 \|j 2023 \|e 9 \|b 16 \|c 02 \|h 1097-1112

Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism

Zugang & Verfügbarkeit

Zugehörige Publikationen/Bände