By Nanna M. Andersen | Published: 07.05.22 | Edited: 02.07.23 | Dansk oversættelse: 13.12.23 A summary of: Decrease of learning capacity in offspring with increasing paternal age in the rat By: Auroux M. Teratology. 1983 Apr;27(2):141-8. In the first experiment, 15 male rats were mated at various ages (2.5, 6, 10, 14, 18, and 22 months) with 2.5-month-old females. In a separate experiment, 15 male rats at 2.5 months and 15 males at 15 months were bred with 2.5-month-old females. The offspring from all groups were evaluated for mean litter size, sex ratio, frequency of malformations, growth patterns, and mortality within the first 13 weeks of life. At 10 to 13 weeks, the offspring's spontaneous activity, emotionality, and learning capacity were also assessed. The study observed a decrease in learning capacity among offspring from older males, particularly male offspring. In male offspring, there was a significant decrease in successful learning capacity when sired by males at 14 months of age. Offspring sired by 18-month-old males exhibited only a 55% successful learning capacity. The percentage further dropped to 45% and 50% when offspring were sired by 22 and 23-month-old males, respectively. These results suggest that breeding males older than 14 months can have a negative impact on the learning capacity of male offspring. It is important to note that these findings are specific to the experimental conditions and may not directly translate to other rat populations or strains. However, they highlight the potential effects of advanced paternal age on offspring learning capacity. A summary of: Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study By: Krug et al. Molecular Autism (2020) 11:54. In this experiment, two groups of rats were used to assess the influence of the age of male rats on offspring behavior. The first group involved 2-month-old female rats bred with either 2-month-old or 12-month-old male rats, resulting in 16 litters. The second group consisted of 2-month-old female rats bred with either 2-month-old or 21-month-old male rats, resulting in 17 litters. Offspring from both groups underwent various behavioral tests to evaluate signs of Autism Spectrum Disorder (ASD), anxiety, depression, schizophrenia, and bipolar disorder. The findings indicated that older males produced offspring that exhibited behavior similar to ASD, including deficits in social communication and repetitive and stereotyped patterns of behavior (e.g., tail-chasing and circling). Heightened anxiety-related behavior during early development was also observed in offspring from older males. Additionally, changes in crucial developmental behaviors, such as rough-and-tumble play, were noted, with offspring from older males emitting fewer pro-social 50-kHz ultrasonic vocalizations (USV) compared to offspring from younger males. Repetitive and stereotyped patterns of behavior were observed at both the motor behavior and higher cognitive levels. Offspring from older males displayed higher levels of anxiety-related behavior, specifically emitting isolation-induced 40-kHz USV. However, no evidence of other behavioral phenotypes such as depression or neurodevelopmental disorders like schizophrenia (SZ) and bipolar disorder (BPD) was observed. Only behavioral alterations linked to ASD were identified, and sucrose preference, used to assess anhedonia-like alterations related to depression, was not affected by the age of the male. Maternal care, known to affect emotion regulation and social development in offspring, was considered as a potential factor influencing the observed behavioral differences. However, the study found no evidence to support differences in maternal care among the groups. Maternal care did not differ across the various breeding conditions. Analysis of microRNA (miRNA) showed no change in pre-miR-132 and pre-miR-134 levels in offspring from older males, but the mature miRNAs (miR-132 and miR-134) were upregulated in these offspring. This suggests potential alterations in gene expression regulation that may contribute to the observed behavioral differences which can then be inherited. References
A summary of: Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring By: Luo, L., Sun, T., Guan, X. et al. Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring. Neurochem Res 42, 2869–2880 (2017). In this experiment, young (3-4 months) and aged (12-14 months) male and female rats were used to test the effects of Chronic Unpredictable Mild Stress (CUMS). The resulting offspring from these breedings were separated into four groups: two groups of male offspring and two groups of female offspring. Group 1 consisted of 4-month-old rats without stress, group 2 included 4-month-old rats exposed to CUMS, group 3 comprised 12-month-old rats without stress, and group 4 consisted of 12-month-old rats exposed to CUMS. Rats from the same mother were assigned to different groups. The CUMS procedure involved subjecting the rats to seven mild stressors over a three-week period: (1) 24-hour food deprivation, (2) 24-hour water deprivation, (3) placement in new cages without sawdust for 24 hours, (4) foot shocks (0.3 mA, 1 second, repeated 15 times), (5) overnight illumination, (6) placement in moist and tilted cages (45°) for 24 hours, and (7) forced swimming at 4°C for 5 minutes. The CUMS treatment was initiated when the rats were 4 weeks old. The results of the study showed that CUMS induced anhedonia (the inability to experience pleasure) and anxiety-like behaviors, as well as impaired learning and memory in both offspring from aged and young parental rats. Female offspring from aged males exhibited impaired learning and memory, as well as a greater increase in corticosterone levels in response to foot electrical shocks. The open field tests revealed clear signs of anxiety-like behavior in the CUMS groups. However, in the open arm test, the results were almost equal for the female groups. Based on these findings, it was concluded that advanced parental age leads to impaired fear memory and spatial memory, predominantly affecting female offspring. The brain regions associated with fear memory and spatial memory may be more susceptible to the effects of advanced parental age in female offspring compared to males. Fædrealder ved avlAf Nanna M. Andersen | Offentliggjort: 13.12.23 | Redigeret: 02.07.23
A summary of: Decrease of learning capacity in offspring with increasing paternal age in the rat By: Auroux M. Teratology. 1983 Apr;27(2):141-8. I det første forsøg blev 15 hanrotter parret i forskellige aldre (2,5, 6, 10, 14, 18 og 22 måneder) med hunrotter på 2,5 måneder. I et separat forsøg blev 15 hanrotter på 2,5 måneder og 15 hanrotter på 15 måneder parret med hunrotter på 2,5 måneder. Afkom fra alle grupper blev evalueret med hensyn til gennemsnitlig kuldstørrelse, kønsfordeling, hyppighed af misdannelser, vækstmønstre og dødelighed inden for de første 13 uger af livet. Ved 10 til 13 uger blev afkommets spontane aktivitet, følelsesmæssighed og indlæringskapacitet også vurderet. Studiet observerede en nedgang i indlæringskapaciteten hos afkom fra ældre hanner, især hanafkom. Hos hanafkom var der en betydelig nedgang i vellykket indlæringskapacitet, når de var avlet af hanner på 14 måneder. Afkom fra 18 måneder gamle hanner viste kun en succesrate på 55% i indlæringsevne. Procentdelen faldt yderligere til 45% og 50%, når afkommet blev avlet af hanner på henholdsvis 22 og 23 måneder. Disse resultater antyder, at avl af hanner ældre end 14 måneder kan have en negativ indvirkning på den indlæringskapacitet, hanafkom kan opnå. Det er vigtigt at bemærke, at disse resultater er specifikke for de eksperimentelle betingelser og muligvis ikke direkte kan overføres til andre rottepopulationer eller stammer. Dog belyser de potentielle virkninger af avanceret fædrealder på afkommets indlæringskapacitet. Et resume af: Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study By: Krug et al. Molecular Autism (2020) 11:54. I dette eksperiment blev to grupper rotter brugt til at vurdere indflydelsen af hannerotters alder på afkommets adfærd. Den første gruppe involverede hunrotter på 2 måneder, der blev parret med enten hanrotter på 2 måneder eller 12 måneder, hvilket resulterede i 16 kuld. Den anden gruppe bestod af hunrotter på 2 måneder, der blev parret med enten hanrotter på 2 måneder eller 21 måneder, hvilket resulterede i 17 kuld. Afkom fra begge grupper blev underkastet forskellige adfærdstests for at evaluere tegn på autismespektrumforstyrrelser (ASD), angst, depression, skizofreni og bipolar lidelse. Resultaterne indikerede, at ældre hanner producerede afkom, der udviste adfærd, der ligner ASD, herunder mangler i social kommunikation og gentagne og stereotypiske adfærdsmønstre (f.eks. halejagt og cirkling). Øget angstrelateret adfærd i tidlig udvikling blev også observeret hos afkom fra ældre hanner. Derudover blev der noteret ændringer i væsentlige udviklingsadfærd, såsom grov-leg, hvor afkom fra ældre hanner udsendte færre pro-sociale 50 kHz ultralydsvokaliseringer (USV) sammenlignet med afkom fra yngre hanner. Gentagne og stereotypiske adfærdsmønstre blev observeret på både motorisk adfærds- og højere kognitive niveauer. Afkom fra ældre hanner viste højere niveauer af angstrelateret adfærd, især udsendelse af 40 kHz USV i isolationsforhold. Der blev dog ikke observeret bevis for andre adfærdsfænotyper som depression eller neurodevelopmentale lidelser som skizofreni (SZ) og bipolar lidelse (BPD). Kun adfærdsændringer forbundet med ASD blev identificeret, og sukkerpræference, brugt til at vurdere anhedonia-lignende ændringer relateret til depression, blev ikke påvirket af hannerens alder. Moderlig pleje, kendt for at påvirke følelsesregulering og social udvikling hos afkom, blev betragtet som en potentiel faktor, der påvirkede de observerede adfærdsforskelle. Imidlertid fandt studiet ingen beviser for forskelle i moderlig pleje mellem grupperne. Moderlig pleje var ensartet på tværs af de forskellige avlsbetingelser. Analyse af mikro-RNA (miRNA) viste ingen ændring i niveauerne af pre-miR-132 og pre-miR-134 i afkom fra ældre hanner, men de modne miRNA'er (miR-132 og miR-134) blev opreguleret hos dette afkom. Dette antyder potentielle ændringer i reguleringen af genekspression, der kan bidrage til de observerede adfærdsforskelle, som derefter kan arves. References
Et resume af: Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring By: Luo, L., Sun, T., Guan, X. et al. Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring. Neurochem Res 42, 2869–2880 (2017). I dette eksperiment blev unge (3-4 måneder) og ældre (12-14 måneder) han- og hunrotter brugt til at teste virkningerne af kronisk uforudsigelig mild stress (CUMS). Afkommet fra disse parrings blev opdelt i fire grupper: to grupper af hanafkom og to grupper af hunafkom. Gruppe 1 bestod af 4 måneder gamle rotter uden stress, gruppe 2 inkluderede 4 måneder gamle rotter udsat for CUMS, gruppe 3 omfattede 12 måneder gamle rotter uden stress, og gruppe 4 bestod af 12 måneder gamle rotter udsat for CUMS. Rotter fra samme mor blev tildelt forskellige grupper. CUMS-proceduren involverede at udsætte rotterne for syv milde stressorer over en tre-ugers periode: (1) 24-timers fødevaredeprivation, (2) 24-timers vanddeprivation, (3) placering i nye bure uden savsmuld i 24 timer, (4) elektriske stød på fødderne (0,3 mA, 1 sekund, gentaget 15 gange), (5) natten over belysning, (6) placering i fugtige og skrå bure (45°) i 24 timer og (7) tvungen svømning ved 4°C i 5 minutter. CUMS-behandlingen blev startet, da rotterne var 4 uger gamle. Resultaterne af studiet viste, at CUMS inducerede anhedoni (manglende evne til at opleve glæde) og angstlignende adfærd samt nedsat indlæring og hukommelse hos afkom fra både ældre og unge forældrerotter. Hunrotteafkom fra ældre hanner viste nedsat indlæring og hukommelse samt en større stigning i kortikosteronniveauer som reaktion på elektriske stød på fødderne. Åbne mark-tests afslørede tydelige tegn på angstlignende adfærd i CUMS-grupperne. Imidlertid var resultaterne næsten ens for de kvindelige grupper i den åbne arm-test. Baseret på disse fund konkluderedes det, at avanceret forældrealder fører til nedsat frygt- og rumlig hukommelse, primært påvirker hunrotteafkom. De hjerneregioner, der er forbundet med frygt- og rumlig hukommelse, kan være mere modtagelige for virkningerne af avanceret forældrealder hos hunrotteafkom sammenlignet med hanner.
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